CN112022738A - Oral mucosa protection plasma-explosion capsule containing hyaluronic acid, preparation method and application thereof - Google Patents
Oral mucosa protection plasma-explosion capsule containing hyaluronic acid, preparation method and application thereof Download PDFInfo
- Publication number
- CN112022738A CN112022738A CN202010951624.7A CN202010951624A CN112022738A CN 112022738 A CN112022738 A CN 112022738A CN 202010951624 A CN202010951624 A CN 202010951624A CN 112022738 A CN112022738 A CN 112022738A
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- China
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- hyaluronic acid
- capsule
- oil
- water
- Prior art date
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- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
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Abstract
The invention discloses an oral mucosa protection plasma-explosion capsule containing hyaluronic acid, a preparation method and application thereof. The oral mucosa protection burst capsule containing hyaluronic acid comprises a capsule skin and contents, wherein the capsule skin comprises hyaluronic acid, gelatin, glycerol and water; the contents comprise oleum Menthae Dementholatum, Mentholum, Borneolum Syntheticum, oleum Eucalypti, oleum Lavandula Angustifolia, lemon essential oil, vitamin C, vitamin E, glycerol, soybean oil, Cera flava and water. The slurry explosion capsule disclosed by the invention can be accurately positioned, and can be used for long-term water replenishing, moisture preserving and oral cavity lubricating.
Description
Technical Field
The invention relates to the technical field of oral care, in particular to an oral mucosa protective plasma-explosion capsule containing hyaluronic acid, a preparation method and application thereof.
Background
Xerostomia is currently very common. Xerostomia, due to its high incidence, WDF defines it as a "modern human disease". About 20% of people in the 20 year old suffer from xerostomia, about 40% of people in the 60 year old suffer from xerostomia, and in higher proportion in older people. Xerostomia also occurs as a side effect of common diseases such as diabetes, cancer, anxiety, depression, allergy, etc.
Relates to an oral care product of hyaluronic acid, which is mainly a liquid preparation and a common film agent. CN 103405470 a discloses a hyaluronic acid composition in the form of a solution for treating and relieving xerostomia. CN 105056219A discloses an artificial saliva containing 0.5mg/ml hyaluronic acid. CN 103462847 a discloses a gargle for oral care. Patent application publication No. CN107536725A discloses a multipurpose oral composition containing a hyaluronic acid mixture and its use, which can be applied to toothpaste, tooth powder, mouthwash, mouth spray. Patent application CN 103211801A discloses a film agent capable of being rapidly dissolved in oral cavity, which is composed of 30-90% of water-soluble film forming material, 2-20% of plasticizer, 0-5% of disintegrating agent and 0.1-70% of medicinal active ingredient. The film forming material is a mixture of hydroxypropyl methylcellulose and hyaluronic acid, the weight ratio is 20-80: 1, and the dosage of the hyaluronic acid is extremely low and is less than 5%.
The most important thing for xerostomia is water replenishing, and the products commonly used for treating xerostomia in the market at present comprise gargle, buccal tablets and common films, and the ubiquitous problem is that the product has short retention time in the oral cavity and cannot play a role in replenishing water and preserving moisture for a long time. In addition, the patch is easy to move or even fall off in the oral cavity, and the positioning is very inaccurate; most of the buccal tablets contain a freshener, so that patients feel no dryness and no itch through cooling feeling, and water is not substantially supplemented.
Disclosure of Invention
In order to solve the problems, the invention provides an oral mucosa protection and plasma explosion capsule containing hyaluronic acid, which can realize accurate positioning and long-acting water replenishing and moisture retention, a preparation method and application thereof.
The specific technical scheme of the invention is as follows:
1. an oral mucosa protection slurry burst capsule containing hyaluronic acid comprises a capsule skin and contents, wherein the capsule skin comprises hyaluronic acid, gelatin, glycerol and water;
the contents comprise oleum Menthae Dementholatum, Mentholum, Borneolum Syntheticum, oleum Eucalypti, oleum Lavandula Angustifolia, lemon essential oil, vitamin C, vitamin E, glycerol, soybean oil, Cera flava and water.
2. The popping capsule of item 1, wherein the capsule shell comprises, in parts by weight, 0.1-3 parts of hyaluronic acid, 10-20 parts of gelatin, 3-10 parts of glycerol and 10-20 parts of water, preferably, the capsule shell comprises 0.6-2 parts of hyaluronic acid, 10-18 parts of gelatin, 3-8 parts of glycerol and 10-18 parts of water, and more preferably, the capsule shell comprises 1.0-1.5 parts of hyaluronic acid, 13-16 parts of gelatin, 4-7 parts of glycerol and 13-16 parts of water.
3. The popping capsule of item 1 or 2, wherein the contents comprise, by weight, 0.5-5 parts of peppermint oil, 0.1-1 part of menthol, 0.1-0.5 part of borneol, 0.5-5 parts of eucalyptus oil, 0.1-1 part of lavender oil, 0.1-1 part of lemon essential oil, 0.001-0.01 part of vitamin C, 0.001-0.01 part of vitamin E, 0.5-2.5 parts of glycerin, 12-23 parts of soybean oil, 0.5-2.5 parts of beeswax, and 1-4 parts of water; preferably, the content comprises 1.5-5 parts of peppermint oil, 0.5-1 part of menthol, 0.3-0.5 part of borneol, 1-5 parts of eucalyptus oil, 0.5-1 part of lavender oil, 0.3-1 part of lemon essential oil, 0.005-0.01 part of vitamin C, 0.006-0.01 part of vitamin E, 0.5-1.5 parts of glycerol, 12-18 parts of soybean oil, 1.5-2.5 parts of beeswax and 2-4 parts of water.
4. The burst capsule according to any one of claims 1 to 3, wherein the hyaluronic acid comprises ultra-low hyaluronic acid, low-molecular hyaluronic acid, high-molecular hyaluronic acid and cross-linked hyaluronic acid, and preferably, the mass ratio of the ultra-low hyaluronic acid, the low-molecular hyaluronic acid, the high-molecular hyaluronic acid and the cross-linked hyaluronic acid is 4-1:3-1:3-1:3-1, and preferably 2:1:1: 1.
5. The popping capsule of item 4 wherein,
the molecular weight of the ultra-low hyaluronic acid is 1k-10kDa, preferably 1k-5kDa, more preferably 1k-3 kDa;
the molecular weight of the low molecular weight hyaluronic acid is 100k-400kDa, preferably 100k-300kDa, more preferably 200k-300 kDa;
the molecular weight of the high molecular hyaluronic acid is 1000k-2000kDa, preferably 1000k-1500kDa, and more preferably 1000k-1300 kDa.
6. The popping capsule of any of claims 1-5 wherein the shape of the capsule is the same as the shape of the palate of the mouth.
7. A method for preparing oral mucosa protection plasma-explosion capsules containing hyaluronic acid comprises the following steps:
mixing hyaluronic acid, gelatin, glycerol and water, and defoaming to obtain capsule skin liquid;
mixing oleum Menthae Dementholatum, Mentholum, Borneolum Syntheticum, oleum Eucalypti, oleum Lavandula Angustifolia, lemon essential oil, vitamin C, vitamin E, glycerol, soybean oil, Cera flava and water to obtain content material liquid;
and pelleting the capsule skin liquid and the content liquid to obtain the capsule.
8. The method according to item 7, wherein the capsule shell comprises 0.1-3 parts of hyaluronic acid, 10-20 parts of gelatin, 3-10 parts of glycerol and 10-20 parts of water by weight, preferably the capsule shell comprises 0.6-2 parts of hyaluronic acid, 10-18 parts of gelatin, 3-8 parts of glycerol and 10-18 parts of water, and further preferably the capsule shell comprises 1.0-1.5 parts of hyaluronic acid, 13-16 parts of gelatin, 4-7 parts of glycerol and 13-16 parts of water.
9. The method according to item 7 or 8, wherein the contents comprise, by weight, 0.5-5 parts of peppermint oil, 0.1-1 part of menthol, 0.1-0.5 part of borneol, 0.5-5 parts of eucalyptus oil, 0.1-1 part of lavender oil, 0.1-1 part of lemon essential oil, 0.001-0.01 part of vitamin C, 0.001-0.01 part of vitamin E, 0.5-2.5 parts of glycerin, 12-23 parts of soybean oil, 0.5-2.5 parts of beeswax, and 1-4 parts of water, preferably, the contents comprise 1.5-5 parts of peppermint oil, 0.5-1 part of menthol, 0.3-0.5 part of borneol, 1-5 parts of eucalyptus oil, 0.5-1 part of lavender oil, 0.3-1 part of lemon essential oil, 0.005-0.01 part of vitamin C, 0.01-0.006 part of vitamin E, 0.5-1.5 parts of glycerol, 12-18 parts of soybean oil, 1.5-2.5 parts of beeswax and 2-4 parts of water.
10. The method according to any one of claims 7 to 9, wherein the hyaluronic acid comprises ultra-low hyaluronic acid, low molecular hyaluronic acid, high molecular hyaluronic acid and cross-linked hyaluronic acid, preferably the mass ratio of ultra-low hyaluronic acid, low molecular hyaluronic acid, high molecular hyaluronic acid and cross-linked hyaluronic acid is 4-1:3-1:3-1:3-1, preferably 2:1:1: 1.
11. The method of item 10, wherein,
the molecular weight of the ultra-low hyaluronic acid is 1k-10kDa, preferably 1k-5kDa, more preferably 1k-3 kDa;
the molecular weight of the low molecular weight hyaluronic acid is 100k-400kDa, preferably 100k-300kDa, more preferably 200k-300 kDa;
the molecular weight of the high molecular hyaluronic acid is 1000k-2000kDa, preferably 1000k-1500kDa, and more preferably 1000k-1300 kDa.
12. The method according to any one of items 7 to 11, wherein, in the step of obtaining the capsule skin liquid, water, hyaluronic acid, glycerin and gelatin are mixed in order, and then dissolved at a temperature ranging from 70 to 80 ℃, followed by deaeration to obtain the capsule skin liquid.
13. The method of clause 12, wherein the debubbling is performed under a vacuum of 0.06M-0.08 Mpa.
14. The method according to any one of items 7 to 13, wherein, in the step of obtaining the content liquid, water and vitamin C are mixed, then glycerin is added, and then peppermint oil, menthol, borneol, eucalyptus oil, lavender oil, lemon essential oil, vitamin E, soybean oil and beeswax are added and mixed, and dissolved at 70 to 80 ℃ to obtain the content liquid.
15. The method according to any one of claims 7 to 14, wherein the pelleting process is carried out by separately feeding the capsule shell solution and the content solution into a soft capsule machine containing a model of the shape of the palate of the mouth, and preferably, the pelleting process is carried out at a temperature of 18 to 26 ℃ and a humidity of 30 to 50%.
16. The method according to item 15, wherein after pelleting, shaping and drying, washing, drying and selecting the pellets are carried out, preferably, the shaping and drying time is 1-2 h;
washing the pills with edible ethanol, preferably with the edible ethanol with the volume concentration of 95%;
the pill airing is carried out under the conditions that the temperature is 20-25 ℃ and the humidity is 25-30%, and preferably, the pill airing time is 24-48 h.
17. The method of item 15, wherein the method of making the oral maxilla shape model comprises the steps of:
and manufacturing an oral cavity contour model, cutting along one half or one third of the upper jaw of the oral cavity contour model in the vertical direction, and obtaining the oral cavity upper jaw shape model through 3D printing conversion.
18. A method of using a capsule comprising placing the capsule of any one of claims 1-6 or the capsule of any one of claims 7-17 in the mouth of a patient in need thereof, and fitting the capsule to the palate of the patient.
19. An oral care product comprising the popping capsule of any one of items 1-6 or the popping capsule prepared by the preparation method of any one of items 7-17.
20. Use of the popping capsules according to any one of items 1 to 6 or the popping capsules prepared by the method according to any one of items 7 to 17 in the field of oral care, preferably in the field of dry mouth care, dry and itchy mouth care or oral ulcer care.
ADVANTAGEOUS EFFECTS OF INVENTION
The slurry explosion capsule disclosed by the invention can be accurately positioned, and can be used for long-term water replenishing, moisture preserving and oral cavity lubricating.
Detailed Description
The present invention will be described in detail below. While specific embodiments of the invention have been shown, it should be understood that the invention may be embodied in various forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art.
It should be noted that certain terms are used throughout the description and claims to refer to particular components. As one skilled in the art will appreciate, various names may be used to refer to a component. This specification and claims do not intend to distinguish between components that differ in name but not function. In the following description and in the claims, the terms "include" and "comprise" are used in an open-ended fashion, and thus should be interpreted to mean "include, but not limited to. The description which follows is a preferred embodiment of the invention, however, the description is given for the purpose of illustrating the general principles of the invention and not for the purpose of limiting the scope of the invention. The scope of the present invention is defined by the appended claims.
The invention provides an oral mucosa protection slurry explosion capsule containing hyaluronic acid, which comprises a capsule skin and contents, wherein the capsule skin comprises hyaluronic acid, gelatin, glycerol and water;
the contents comprise oleum Menthae Dementholatum, Mentholum, Borneolum Syntheticum, oleum Eucalypti, oleum Lavandula Angustifolia, lemon essential oil, vitamin C, vitamin E, glycerol, soybean oil, Cera flava and water.
The oral mucosa protection slurry explosion capsule explodes slurry at the upper jaw position of the oral cavity, so that the oral mucosa is protected.
Hyaluronic Acid (HA), also known as Hyaluronic acid, is a long-chain polymeric mucopolysaccharide formed by alternating arrangement of D-glucuronic acid and N-acetylglucosamine, is widely distributed in various parts of a human body, HAs good hydrophilicity, viscoelasticity, lubricity and biocompatibility, and is widely applied in the medical field.
The gelatin is a tasteless, colorless (slightly yellowish), translucent, hard amorphous substance, insoluble in organic solvents, highly water-absorbent and highly viscous. Gelatin is a polymeric substance of peptide molecules and is a hydrolysate of collagen. Gelatin is one of the main components of the soft capsule shell, and the gelatin power used by the invention is 180.
The peppermint oil is also called peppermint extract, is mainly used for oral hygiene products such as toothpaste and tooth powder, is used as a medicament for cooling, dispelling wind, diminishing inflammation, easing pain and exciting in certain medicines, and can also be used in after-shave products, certain cosmetics, tobacco and food.
The menthol is a saturated cyclic alcohol obtained from oleum Menthae Dementholatum, and has effects of refreshing and relieving itching, relieving sore throat and laryngitis, and has special fragrance of herba Menthae, and is very soluble in ethanol, chloroform, diethyl ether, liquid paraffin or volatile oil, and very slightly soluble in water.
The borneol, named as borneol, orange slice, blumea balsamifera, borneol, plum blossom borneol, tomatillo castanea, plum blossom camphor, bornyl alcohol, plum blossom ice and the like, is obtained by steam distillation and recrystallization of stems and leaves of blumea balsamifera of Compositae or branches and leaves of camphor of Lauraceae, has the functions of clearing heat, relieving pain and relieving swelling, and is soluble in ethanol, chloroform, gasoline or ether and almost insoluble in water.
The eucalyptus oil is also called cajeput and eucalyptol, is colorless oily liquid, is extracted from substances such as eucalyptus oil, cajeput oil, camphor oil, bay leaf oil and the like, is widely used for medicines, is prepared into toothpaste essence and the like, has special cool and refreshing eucalyptus spinosa leaf fragrance, has a few of camphor odor, has medicinal gas, has pungent and refreshing feeling, strong and non-lasting fragrance, has certain mildew-proof, sterilization and corrosion-proof effects, is almost insoluble in water, and is dissolved in ethanol, absolute ethanol, oil and fat.
The lavender oil is extracted from lavender, and has the functions of clearing away heat and toxic materials, cleaning mucous membranes or skin, promoting regeneration and recovery of damaged tissues and the like.
The lemon essential oil has fresh fragrance of lemon, and can refresh brain, refresh mind, relieve dysphoria and purify air. The lemon essential oil also has a lot of positive conditioning effects on the skin and the body.
The beeswax is wax secreted by four pairs of wax glands at the abdomen of a bee (worker bee), is in a solid state at normal temperature, and is a common suspension stabilizer for soft capsules.
The water may be, for example, purified water.
In a preferred embodiment of the present invention, wherein the capsule skin comprises 0.1-3 parts of hyaluronic acid, 10-20 parts of gelatin, 3-10 parts of glycerol and 10-20 parts of water by weight, preferably the capsule skin comprises 0.6-2 parts of hyaluronic acid, 10-18 parts of gelatin, 3-8 parts of glycerol and 10-18 parts of water, and further preferably the capsule skin comprises 1.0-1.5 parts of hyaluronic acid, 13-16 parts of gelatin, 4-7 parts of glycerol and 13-16 parts of water.
For example, the hyaluronic acid may be 0.1 parts, 0.6 parts, 1 part, 1.2 parts, 1.5 parts, 2 parts, 2.5 parts, 3 parts, or any range therebetween, by weight part;
the gelatin may be 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15 parts, 16 parts, 17 parts, 18 parts, 19 parts, 20 parts or any range therebetween;
the glycerol may be 3 parts, 4 parts, 5 parts, 6 parts, 7 parts, 8 parts, 9 parts, 10 parts, or any range therebetween;
the water may be 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15 parts, 16 parts, 17 parts, 18 parts, 19 parts, 20 parts, or any range therebetween.
In a preferred embodiment of the present invention, wherein the capsule skin is composed of hyaluronic acid, gelatin, glycerol and water;
preferably, the capsule shell consists of 0.1 to 3 parts of hyaluronic acid, 10 to 20 parts of gelatin, 3 to 10 parts of glycerol and 10 to 20 parts of water by weight, preferably, the capsule shell consists of 0.6 to 2 parts of hyaluronic acid, 10 to 18 parts of gelatin, 3 to 8 parts of glycerol and 10 to 18 parts of water, and more preferably, the capsule shell consists of 1.0 to 1.5 parts of hyaluronic acid, 13 to 16 parts of gelatin, 4 to 7 parts of glycerol and 13 to 16 parts of water by weight.
In a preferred embodiment of the present invention, the content comprises, by weight, 0.5 to 5 parts of peppermint oil, 0.1 to 1 part of menthol, 0.1 to 0.5 part of borneol, 0.5 to 5 parts of eucalyptus oil, 0.1 to 1 part of lavender oil, 0.1 to 1 part of lemon essential oil, 0.001 to 0.01 part of vitamin C, 0.001 to 0.01 part of vitamin E, 0.5 to 2.5 parts of glycerin, 12 to 23 parts of soybean oil, 0.5 to 2.5 parts of beeswax and 1 to 4 parts of water; preferably, the content comprises 1.5-5 parts of peppermint oil, 0.5-1 part of menthol, 0.3-0.5 part of borneol, 1-5 parts of eucalyptus oil, 0.5-1 part of lavender oil, 0.3-1 part of lemon essential oil, 0.005-0.01 part of vitamin C, 0.006-0.01 part of vitamin E, 0.5-1.5 parts of glycerol, 12-18 parts of soybean oil, 1.5-2.5 parts of beeswax and 2-4 parts of water.
For example, the peppermint oil may be 0.5 parts, 1 part, 1.5 parts, 2 parts, 2.5 parts, 3 parts, 3.5 parts, 4 parts, 4.5 parts, 5 parts, or any range therebetween;
the menthol may be 0.1 part, 0.2 part, 0.3 part, 0.4 part, 0.5 part, 0.6 part, 0.7 part, 0.8 part, 0.9 part, 1 part or any range therebetween;
the borneol can be 0.1 part, 0.2 part, 0.3 part, 0.4 part, 0.5 part or any range therebetween;
the eucalyptus oil can be 0.5 part, 1 part, 1.5 parts, 2 parts, 2.5 parts, 3 parts, 3.5 parts, 4 parts, 4.5 parts, 5 parts or any range therebetween;
the lavender oil can be 0.1 part, 0.2 part, 0.3 part, 0.4 part, 0.5 part, 0.6 part, 0.7 part, 0.8 part, 0.9 part, 1 part or any range therebetween;
the lemon essential oil can be 0.1 part, 0.2 part, 0.3 part, 0.4 part, 0.5 part, 0.6 part, 0.7 part, 0.8 part, 0.9 part, 1 part or any range therebetween;
the vitamin C can be 0.001 parts, 0.002 parts, 0.003 parts, 0.004 parts, 0.005 parts, 0.006 parts, 0.007 parts, 0.008 parts, 0.009 parts, 0.01 parts or any range therebetween;
the vitamin E can be 0.001 parts, 0.002 parts, 0.003 parts, 0.004 parts, 0.005 parts, 0.006 parts, 0.007 parts, 0.008 parts, 0.009 parts, 0.01 parts, or any range therebetween;
the glycerol may be 0.5 parts, 1 part, 1.5 parts, 2 parts, 2.5 parts, or any range therebetween;
the soybean oil can be 12 parts, 13 parts, 14 parts, 15 parts, 16 parts, 17 parts, 18 parts, 19 parts, 20 parts, 21 parts, 22 parts, 23 parts or any range therebetween;
the beeswax may be 0.5 parts, 1 part, 1.5 parts, 2 parts, 2.5 parts or any range therebetween;
the water may be 1 part, 2 parts, 3 parts, 4 parts, or any range therebetween.
In a preferred embodiment of the present invention, wherein the content comprises peppermint oil, menthol, borneol, eucalyptus oil, lavender oil, lemon essential oil, vitamin C, vitamin E, glycerin, soybean oil, beeswax and water;
preferably, the content comprises, by weight, 0.5-5 parts of peppermint oil, 0.1-1 part of menthol, 0.1-0.5 part of borneol, 0.5-5 parts of eucalyptus oil, 0.1-1 part of lavender oil, 0.1-1 part of lemon essential oil, 0.001-0.01 part of vitamin C, 0.001-0.01 part of vitamin E, 0.5-2.5 parts of glycerol, 12-23 parts of soybean oil, 0.5-2.5 parts of beeswax and 1-4 parts of water; preferably, the content consists of 1.5-5 parts of peppermint oil, 0.5-1 part of menthol, 0.3-0.5 part of borneol, 1-5 parts of eucalyptus oil, 0.5-1 part of lavender oil, 0.3-1 part of lemon essential oil, 0.005-0.01 part of vitamin C, 0.006-0.01 part of vitamin E, 0.5-1.5 parts of glycerol, 12-18 parts of soybean oil, 1.5-2.5 parts of beeswax and 2-4 parts of water.
In a preferred embodiment of the present invention, the hyaluronic acid comprises ultra-low hyaluronic acid, low-molecular hyaluronic acid, high-molecular hyaluronic acid and cross-linked hyaluronic acid, and preferably, the mass ratio of the ultra-low hyaluronic acid, the low-molecular hyaluronic acid and the high-molecular hyaluronic acid to the cross-linked hyaluronic acid (i.e. the mass ratio of the ultra-low hyaluronic acid/the low-molecular hyaluronic acid/the high-molecular hyaluronic acid/the cross-linked hyaluronic acid) is 4-1:3-1:3-1:3-1, preferably 2:1:1: 1.
For example, the mass ratio of the ultra-low hyaluronic acid, the low-molecular hyaluronic acid, the high-molecular hyaluronic acid and the cross-linked hyaluronic acid may be 4:3:3:3, 4:3:3:2, 4:3:3:1, 4:3:2:3, 4:3:1:3, 4:3:2:2, 4:3:2:1, 4:3:1:1, 4:2:3:3, 4:2:2:3, 4:2:1:3, 4:2:3:2, 4:2:3:1, 3:2:3:3, 3:1:3:3, 3:2:2:2, 3:1:3:1, 1:1:3:3, 2:1:1, 1:1:3:3, etc
The ultra-low hyaluronic acid has extremely low molecular weight, can be absorbed through skin, and improves the expression level of the mucosal aquaporin;
the low molecular hyaluronic acid is hyaluronic acid with relatively low molecular weight, shows very strong biological activity, has the functions of repairing damaged cells, enhancing the antiviral capacity of oral cavity and mucous membrane tissues, inhibiting tumor diffusion, promoting wound healing, promoting bone and angiogenesis, regulating immunity and the like, is easy to permeate into dermis, and is an activator of immune cells and cytokines;
the high molecular weight hyaluronic acid has high molecular weight, can increase the hydration of mucous membrane tissues and quickly improve the water content of mucous membranes of oral cavity and throat;
the cross-linked hyaluronic acid is a derivative formed by chemically modifying hyaluronic acid, the molecular weight of the cross-linked hyaluronic acid can be improved, the water solubility is changed, a physical protective barrier is formed by a mucous membrane layer, the water evaporation in the mucous membrane of the oral cavity and the throat is inhibited, the dryness symptom is relieved, and the clinical effect is improved.
HA with 4 different molecular weights is added to form a compact three-dimensional net structure, a 'water storage sponge' is formed on the surface of a mucous membrane, and continuous protection and water supplement are realized.
The mass ratio of the ultra-low hyaluronic acid, the low molecular hyaluronic acid, the high molecular hyaluronic acid and the cross-linked hyaluronic acid can be, for example, 4-1:3-1:3-1:3-1, and preferably 2:1:1: 1.
In a preferred embodiment of the present invention, wherein,
the molecular weight of the ultra-low hyaluronic acid is 1k-10kDa, preferably 1k-5kDa, more preferably 1k-3 kDa;
the molecular weight of the low molecular weight hyaluronic acid is 100k-400kDa, preferably 100k-300kDa, more preferably 200k-300 kDa;
the molecular weight of the high molecular hyaluronic acid is 1000k-2000kDa, preferably 1000k-1500kDa, and more preferably 1000k-1300 kDa.
For example, the ultra-low hyaluronic acid may have a molecular weight of 1kDa, 2kDa, 3kDa, 4kDa, 5kDa, 6kDa, 7kDa, 8kDa, 9kDa, 10kDa, or the like;
the molecular weight of the low molecular hyaluronic acid can be 100kDa, 150kDa, 200kDa, 250kDa, 300kDa, 350kDa, 400kDa and the like;
the high molecular hyaluronic acid can be 1000kDa, 1200kDa, 1300kDa, 1400kDa, 1500kDa, 1600kDa, 1700kDa, 1800kDa, 1900kDa, 2000kDa and the like.
Wherein "kDa" is 1000Da and is a unit of the weight average molecular weight of hyaluronic acid.
In a preferred embodiment of the invention, wherein the capsule has the same shape as the shape of the palate of the mouth.
The shape of the capsule is designed to be very well matched with the required part, so that the capsule can be accurately positioned and accurately acted.
The invention provides a method for preparing oral mucosa protection plasma-explosion capsules containing hyaluronic acid, which comprises the following steps:
mixing hyaluronic acid, gelatin, glycerol and water, and defoaming to obtain capsule skin liquid;
mixing oleum Menthae Dementholatum, Mentholum, Borneolum Syntheticum, oleum Eucalypti, oleum Lavandula Angustifolia, lemon essential oil, vitamin C, vitamin E, glycerol, soybean oil, Cera flava and water to obtain content material liquid;
and pelleting the capsule skin liquid and the content liquid to obtain the capsule.
In a preferred embodiment of the present invention, in the step of obtaining the capsule skin liquid, water, hyaluronic acid, glycerol and gelatin are sequentially mixed, and then dissolved at a temperature of 70 to 80 ℃, followed by deaeration to obtain the capsule skin liquid. For example, purified water, hyaluronic acid, glycerin and gelatin are sequentially put into a gelatin melting tank, heated for 30 minutes until the temperature ranges from 70 ℃ to 80 ℃, and kept for 30 minutes, so that hyaluronic acid is dissolved and gelatin is swelled.
The temperature is, for example, 70 ℃, 71 ℃, 72 ℃, 73 ℃, 74 ℃, 75 ℃, 76 ℃, 77 ℃, 78 ℃, 79 ℃, 80 ℃ and the like.
In a preferred embodiment of the present invention, wherein the defoaming is performed under a vacuum of 0.06M to 0.08 MPa. For example, the degree of vacuum may be 0.06MPa, 0.07MPa or 0.08 MPa.
In a more preferable embodiment of the invention, in the step of obtaining the capsule shell liquid, purified water, hyaluronic acid, glycerol and gelatin are sequentially put into a gelatin melting tank, heated for 30 minutes until the temperature range is 70-80 ℃, and kept for 30 minutes, after the hyaluronic acid is completely dissolved and the gelatin is completely swelled without particles, air bubbles in the gelatin liquid are removed under the vacuum degree of 0.06-0.08Mpa, the gelatin liquid is discharged through a 80-mesh screen, and kept for later use at 50-60 ℃.
In a preferred embodiment of the present invention, in the step of obtaining the content liquid, water and vitamin C are mixed, then glycerin is added, and then peppermint oil, menthol, borneol, eucalyptus oil, lavender oil, lemon essential oil, vitamin E, soybean oil and beeswax are added and mixed, and dissolved at 70 to 80 ℃ to obtain the content liquid, and the dissolution is performed at 70 ℃, 71 ℃, 72 ℃, 73 ℃, 74 ℃, 75 ℃, 76 ℃, 77 ℃, 78 ℃, 79 ℃ and 80 ℃, for example.
In a more preferable embodiment of the invention, in the step of obtaining the content material liquid, water and vitamin C are placed in a mixing tank, then glycerin is added, finally peppermint oil, menthol, borneol, eucalyptus oil, lavender oil, lemon essential oil, vitamin E, soybean oil and beeswax are added, the temperature is raised to 70-80 ℃, the mixture is dissolved, stirred and uniformly mixed, and the mixed oil material is obtained after cooling; then grinding for 2-3 times by using a colloid mill to uniformly mix the materials to obtain the content of the slurry blasting ball for later use.
In a preferred embodiment of the present invention, the pelleting process comprises putting the capsule shell liquid and the content liquid into a soft capsule machine containing an oral cavity maxilla shape model, and pelleting, preferably, the pelleting process is performed under the conditions that the temperature is 18-26 ℃ and the humidity is 30-50%.
For example, the temperature can be 18 ℃, 19 ℃, 20 ℃, 21 ℃, 22 ℃, 23 ℃, 24 ℃, 25 ℃, 26 ℃ or any range therebetween;
the humidity may be 30%, 35%, 40%, 45%, 50%, or any range therebetween.
In a more preferred embodiment of the present invention, the pelleting process comprises the steps of respectively feeding the content liquid and the capsule skin liquid into a soft capsule machine containing the oral palate shape model at a temperature of 18-26 ℃ and a humidity of 30-50% to pellet; then the produced capsules are shaped and dried for 1-2 hours by a rolling cage type drying machine matched with the soft capsule machine, and then are taken out of the cage, and are placed in a small drying tray and temporarily stored in a pre-drying room.
In a preferred embodiment of the present invention, wherein, in the pelleting process, the pressing force is one half to three quarters of the pressing force of the normal soft capsule.
In a preferred embodiment of the present invention, after the pelleting process, performing shaping drying, washing, airing and selecting, preferably, the shaping drying time is 1-2 h;
washing the pills with edible ethanol, preferably with the edible ethanol with the volume concentration of 95%;
the pill airing is carried out under the conditions that the temperature is 20-25 ℃ and the humidity is 25-30%, and preferably, the pill airing time is 24-48 h.
For example, the setting and drying time is 1h, 1.5h, 2h and the like;
the air-drying pill temperature can be 20 deg.C, 21 deg.C, 22 deg.C, 23 deg.C, 24 deg.C, 25 deg.C, etc.;
humidity can be 25%, 26%, 27%, 28%, 29%, 30%, etc.;
the pill airing time can be 24h, 25h, 26h, 27h, 28h, 29h, 30h, 31h, 32h, 33h, 34h, 35h, 36h, 37h, 38h, 39h, 40h, 41h, 42h, 43h, 44h, 45h, 46h, 47h, 48h and the like.
In a preferred embodiment of the present invention, the method for preparing the shape model of the oral palate comprises the following steps:
the method comprises the steps of manufacturing an oral cavity outline model by using hydrophilic silica gel as an oral cavity impression material, cutting the oral cavity outline model along one half or one third of the upper jaw of the oral cavity outline model in the vertical direction, and converting the oral cavity outline model into the oral cavity upper jaw shape model through 3D printing.
The hydrophilic silicone rubber for the oral impression material can be AFFINIS Mono body, ZEROSIL mono, Oranwash VL, for example, which have been disclosed in the wettability study of "hydrophilic" silicone rubber oral impression materials (Suilaiz et al, wettability study of "hydrophilic" silicone rubber oral impression materials, journal of International department of stomatology, 2009, 36 (4): 405-.
The invention provides a method for using a capsule for popping milk, which comprises the steps of putting the capsule for popping milk into the oral cavity of a patient in need thereof, and enabling the capsule for popping milk to be attached to the upper jaw position of the oral cavity of the patient.
In a more preferred embodiment of the invention, the use method of the slurry explosion capsule comprises the following steps: the oral mucosa protection plasma-explosion capsule containing hyaluronic acid is placed in an inlet, residual water and saliva in the mouth can be absorbed by the plasma-explosion capsule, the water-absorbing spherical surface becomes smooth, the abnormal smooth plasma-explosion capsule can automatically slide to the corresponding position of the oral cavity, and the smooth plasma-explosion capsule is very easily matched with the contour of the oral cavity due to the fact that the shape of the plasma-explosion capsule is customized according to the contour of the oral cavity, the positioning is very accurate, and the matching degree is very high. When the plasma-enhanced capsule reaches a designated position, the plasma-enhanced capsule is always contained, the gaps among hyaluronic acid molecules become larger along with the absorption of water in saliva by hyaluronic acid, small molecules acting in the capsule penetrate through the capsule skin to enter mucous membrane capillaries to take effect, and redundant unabsorbed components are carried on the hyaluronic acid capsule skin to wait for slow release. Along with excessive saliva absorption of hyaluronic acid, partial hyaluronic acid is dissolved, the capsule skin is broken, the unabsorbed and unaffiliated content is spitted, the oral administration takes effect, and the undissolved hyaluronic acid capsule skin still adheres to the appointed position.
The invention provides an oral care product which comprises the above-mentioned capsule or the capsule prepared by the above-mentioned method.
The invention provides an application of the above-mentioned popping capsule or the popping capsule prepared by the above-mentioned method in the oral care field, preferably an application in the oral dry care, the oral dry itch care or the oral ulcer care field.
The oral cavity paste-blasting capsule is prepared by using an oral cavity palate shape model, can be well matched with a required part, can be accurately positioned, and can be used for long-acting water replenishing, moisturizing and lubricating an oral cavity due to the fact that a capsule skin contains hyaluronic acid;
the quick-frozen soybean milk capsules have good moisturizing effect, the moisturizing time is more than 35min, the average curing time is more, the curing rate is below 30d and the curing rate is high at more than 40% after 15 d.
Examples
The invention is described generally and/or specifically for the materials used in the tests and the test methods, in the following examples,% means wt%, i.e. percent by weight, unless otherwise specified. The reagents or instruments used are not indicated by the manufacturer, and are all conventional reagent products commercially available, wherein Table 1 is a source of raw materials used in the examples.
Table 1 sources of raw materials used in the examples
Raw materials | Type/purity | Manufacturer of the product |
Ultra-low hyaluronic acid | 97.1% | BLOOMAGE BIOTECH Co.,Ltd. |
Low molecular weight hyaluronic acid | 98.0% | BLOOMAGE BIOTECH Co.,Ltd. |
High molecular hyaluronic acid | 96.9% | BLOOMAGE BIOTECH Co.,Ltd. |
Cross-linked hyaluronic acid | 97.2% | BLOOMAGE BIOTECH Co.,Ltd. |
Mint oil | 32% | Jiangxisen sea plant oil Co., Ltd |
Menthol crystal | 99% | Jiangxisen sea plant oil Co., Ltd |
Borneol (borneol) | 99% | Guizhou Songjia Biotech Co., Ltd |
Eucalyptus oil | 80% | Jiangxisen sea plant oil Co., Ltd |
Lavender oil | 60% | Jiangxisen sea plant oil Co., Ltd |
Lemon essential oil | 60% | Jiangxisen sea plant oil Co., Ltd |
Vitamin C | 99% | Suzhou Fulaide Biotechnology Ltd |
Vitamin E | 99% | Suzhou Fulaide Biotechnology Ltd |
Soybean oil | -- | Shandong Fuzekang food oil Co., Ltd |
Glycerol | 99% | Henan Hao Xuan chemical products Co., Ltd |
Beeswax (Cera flava) | -- | Dongguanhongnuo wax industry |
Example 1
1. Making an oral cavity maxilla shape mould: firstly, obtaining an oral cavity contour model by adopting AFFINIS monoBody oral cavity impression material hydrophilic silicone rubber, cutting the oral cavity contour model along one third of the upper jaw vertical direction of the oral cavity contour model, and converting the oral cavity contour model into a ceramic model through 3D printing to obtain an oral cavity upper jaw shape model.
2. Preparing capsule shell liquid: putting 20kg of purified water, 0.1kg of hyaluronic acid, 10kg of glycerol and 20kg of gelatin into a gelatin melting tank in sequence, heating and heating for 30 minutes until the temperature is 70 ℃, keeping the temperature for 30 minutes, after the hyaluronic acid is completely dissolved and the gelatin is completely swelled and HAs no particles, pumping out bubbles and removing vacuum, and discharging the gelatin through a 80-mesh pharmacopeia standard screen to obtain capsule skin liquid, and keeping the temperature at 50 ℃ for later use, wherein the hyaluronic acid is a mixture of HA with the molecular weight of 10kDa, low-molecular HA with the molecular weight of 400kDa, high-molecular HA with the molecular weight of 2000kDa and crosslinked HA, and the mass ratio of the ultra-low HA, the low-molecular HA, the high-molecular HA and the crosslinked HA is 1:1:3: 3.
3. Preparation of content material liquid: putting 4kg of purified water and 0.01kg of vitamin C into a mixing tank, then adding 2.5kg of glycerol, then adding 0.5kg of peppermint oil, 0.1kg of menthol, 0.1kg of borneol, 0.5kg of eucalyptus oil, 0.1kg of lavender oil, 0.1kg of lemon essential oil, 0.01kg of vitamin E, 23kg of soybean oil and 0.5kg of beeswax, heating to 70 ℃, dissolving, stirring, mixing uniformly, and cooling to obtain mixed oil; grinding with colloid mill for 2 times to mix materials uniformly to obtain material liquid.
4. Preparing the slurry-blasting capsule: respectively putting the capsule skin liquid obtained in the step 2 and the content liquid obtained in the step 3 into a soft capsule machine (RJN-65 type soft capsule machine, Jinan flying mechanical equipment limited company) containing the oral cavity palate-shaped mould obtained in the step 1 under the environment of 18 ℃ and 30% of humidity to be pressed into pills, wherein the extrusion force is three fourths of that of a common soft capsule to obtain slurry explosion capsules, then carrying out shaping and drying on the produced slurry explosion capsules for 1 hour by a rolling cage type drying machine matched with the soft capsule machine, then taking out the capsules from a cage, washing the pills by edible ethanol with the volume fraction of 95%, airing the pills at the temperature of 20 ℃ and the humidity of 25% for 24 hours, then carrying out pill selection, and placing the finally selected slurry explosion capsules in a small drying tray to be temporarily stored in a pre-drying room for later use.
Example 2
1. Making an oral cavity maxilla shape mould: firstly, obtaining an oral cavity contour model by adopting AFFINIS monoBody oral cavity impression material hydrophilic silicone rubber, cutting the oral cavity contour model along one third of the upper jaw vertical direction of the oral cavity contour model, and converting the oral cavity contour model into a ceramic model through 3D printing to obtain an oral cavity upper jaw shape model.
2. Preparing capsule shell liquid: putting 10kg of purified water, 3kg of hyaluronic acid, 3kg of glycerol and 10kg of gelatin into a gelatin melting tank in sequence, heating and heating for 30 minutes until the temperature is 80 ℃, keeping the temperature for 30 minutes, after the hyaluronic acid is completely dissolved and the gelatin is completely swelled and HAs no particles, pumping out bubbles under the vacuum degree of 0.08Mpa, relieving the vacuum, and discharging the gelatin through a pharmacopeia standard screen of 80 meshes to obtain capsule skin liquid, and keeping the temperature at 60 ℃ for later use, wherein the hyaluronic acid is a mixture of ultralow HA with the molecular weight of 1kDa, low-molecular HA with the molecular weight of 100kDa, high-molecular HA with the molecular weight of 1000kDa and crosslinked HA, and the mass ratio of the ultralow HA, the low-molecular HA, the high-molecular HA and the crosslinked HA is 4:3:1: 1.
3. Preparation of content material liquid: placing 1kg of purified water and 0.001kg of vitamin C into a mixing tank, then adding 0.5kg of glycerol, then adding 5kg of peppermint oil, 1kg of menthol, 0.5kg of borneol, 5kg of eucalyptus oil, 1kg of lavender oil, 1kg of lemon essential oil, 0.001kg of vitamin E, 12kg of soybean oil and 2.5kg of beeswax, heating to 80 ℃, dissolving, stirring uniformly, and cooling to obtain a mixed oil material; grinding with colloid mill for 3 times to mix materials uniformly to obtain material liquid.
4. Preparing the slurry-blasting capsule: and (2) respectively putting the capsule skin liquid obtained in the step (2) and the content liquid obtained in the step (3) into a soft capsule machine containing the oral cavity palate-shaped mold obtained in the step (1) under the environment of 26 ℃ and 50% of humidity to be pressed into pills, wherein the extrusion force is three quarters of that of a common soft capsule to obtain slurry explosion capsules, then carrying out shaping and drying on the produced slurry explosion capsules for 2 hours by a rolling cage type drying machine matched with the soft capsule machine, then taking out the capsules, washing the pills by edible ethanol with the volume fraction of 95%, airing the pills at the temperature of 25 ℃ and the humidity of 30% for 48 hours, then carrying out pill selection, and placing the finally selected slurry explosion capsules in a small drying tray to be temporarily stored in a pre-drying room for later use.
Example 3
1. Making an oral cavity maxilla shape mould: firstly, obtaining an oral cavity contour model by adopting AFFINIS monoBody oral cavity impression material hydrophilic silicone rubber, cutting the oral cavity contour model along one third of the upper jaw vertical direction of the oral cavity contour model, and converting the oral cavity contour model into a ceramic model through 3D printing to obtain an oral cavity upper jaw shape model.
2. Preparing capsule shell liquid: putting 15kg of purified water, 1.2kg of hyaluronic acid, 6kg of glycerol and 15kg of gelatin into a gelatin melting tank in sequence, heating and heating for 30 minutes until the temperature is 75 ℃, keeping the temperature for 30 minutes, after the hyaluronic acid is completely dissolved and the gelatin is completely swelled and HAs no particles, pumping out bubbles and removing vacuum, and discharging the gelatin through a 80-mesh pharmacopeia standard screen to obtain capsule skin liquid, and keeping the temperature at 55 ℃ for later use, wherein the hyaluronic acid is a mixture of ultralow HA with the molecular weight of 3kDa, low-molecular HA with the molecular weight of 200kDa, high-molecular HA with the molecular weight of 1300kDa and crosslinked HA, and the mass ratio of the ultralow HA, the low-molecular HA, the high-molecular HA and the crosslinked HA is 2:1:1: 1.
3. Preparation of content material liquid: putting 2kg of purified water and 0.005kg of vitamin C into a mixing tank, then adding 1.5kg of glycerol, then adding 1.5kg of peppermint oil, 0.5kg of menthol, 0.3kg of borneol, 1kg of eucalyptus oil, 0.5kg of lavender oil, 0.3kg of lemon essential oil, 0.006kg of vitamin E, 18kg of soybean oil and 1.5kg of beeswax, heating to 75 ℃, dissolving, stirring, mixing uniformly, and cooling to obtain a mixed oil material; grinding with colloid mill for 3 times to mix materials uniformly to obtain material liquid.
4. Preparing the slurry-blasting capsule: and (2) respectively putting the capsule skin liquid obtained in the step (2) and the content liquid obtained in the step (3) into a soft capsule machine containing the oral cavity maxilla-shaped die obtained in the step (1) under the environment of 23 ℃ and 40% of humidity to be pressed into pills, wherein the extrusion force is three quarters of that of a common soft capsule to obtain pulp-popping capsules, then carrying out shaping and drying on the produced pulp-popping capsules for 1.5 hours by a rolling cage type drying machine matched with the soft capsule machine, then taking out the capsules from a cage, washing the pills by adopting edible ethanol with the volume fraction of 95%, airing the pills at the temperature of 23 ℃ and the humidity of 28% for 40 hours, then carrying out pill selection, and placing the finally selected pulp-popping capsules in a small drying tray and temporarily storing the capsules in a pre-drying room for later use.
Example 4
1. Making an oral cavity maxilla shape mould: firstly, obtaining an oral cavity contour model by adopting AFFINIS monoBody oral cavity impression material hydrophilic silicone rubber, cutting the oral cavity contour model along one third of the upper jaw vertical direction of the oral cavity contour model, and converting the oral cavity contour model into a ceramic model through 3D printing to obtain an oral cavity upper jaw shape model.
2. Preparing capsule shell liquid: putting 13kg of purified water, 1.5kg of hyaluronic acid, 4kg of glycerol and 13kg of gelatin into a gelatin melting tank in sequence, heating and heating for 30 minutes until the temperature is 75 ℃, keeping the temperature for 30 minutes, after the hyaluronic acid is completely dissolved and the gelatin is completely swelled and HAs no particles, pumping out bubbles and removing vacuum, and discharging the gelatin through a 80-mesh pharmacopeia standard screen to obtain capsule skin liquid, and keeping the temperature at 60 ℃ for later use, wherein the hyaluronic acid is a mixture of ultra-low HA with the molecular weight of 1kDa, low-molecular HA with the molecular weight of 300kDa, high-molecular HA with the molecular weight of 1000kDa and cross-linked HA, and the mass ratio of the ultra-low HA, the low-molecular HA, the high-molecular HA and the cross-linked HA is 1:1:2: 2.
3. Preparation of content material liquid: putting 3kg of purified water and 0.009kg of vitamin C into a mixing tank, then adding 1kg of glycerol, then adding 5kg of peppermint oil, 1kg of menthol, 0.5kg of borneol, 5kg of eucalyptus oil, 0.8kg of lavender oil, 0.8kg of lemon essential oil, 0.009kg of vitamin E, 15kg of soybean oil and 2kg of beeswax, heating to 80 ℃, dissolving, stirring, mixing uniformly, and cooling to obtain a mixed oil material; grinding with colloid mill for 3 times to mix materials uniformly to obtain material liquid.
4. Preparing the slurry-blasting capsule: and (2) respectively putting the capsule skin liquid obtained in the step (2) and the content liquid obtained in the step (3) into a soft capsule machine containing the oral cavity palate-shaped mold obtained in the step (1) under the environment of 18 ℃ and 30% of humidity to be pressed into pills, wherein the extrusion force is three quarters of that of a common soft capsule to obtain slurry explosion capsules, then carrying out shaping and drying on the produced slurry explosion capsules for 2 hours by a rolling cage type drying machine matched with the soft capsule machine, then taking out the capsules, washing the pills by adopting edible ethanol with the volume fraction of 95%, airing the pills at the temperature of 23 ℃ and the humidity of 28% for 36 hours, then carrying out pill selection, and placing the finally selected slurry explosion capsules in a small drying tray and temporarily storing the capsules in a pre-drying room for later use.
Example 5
1. Making an oral cavity maxilla shape mould: firstly, obtaining an oral cavity contour model by adopting AFFINIS monoBody oral cavity impression material hydrophilic silicone rubber, cutting the oral cavity contour model along one third of the upper jaw vertical direction of the oral cavity contour model, and converting the oral cavity contour model into a ceramic model through 3D printing to obtain an oral cavity upper jaw shape model.
2. Preparing capsule shell liquid: putting 16kg of purified water, 1kg of hyaluronic acid, 7kg of glycerol and 16kg of gelatin into a gelatin melting tank in sequence, heating and heating for 30 minutes until the temperature is 70 ℃, keeping the temperature for 30 minutes, after the hyaluronic acid is completely dissolved and the gelatin is completely swelled and HAs no particles, pumping out bubbles under the vacuum degree of 0.06Mpa, relieving the vacuum, and discharging the gelatin through a pharmacopeia standard screen of 80 meshes to obtain capsule skin liquid, and keeping the temperature at 55 ℃ for later use, wherein the hyaluronic acid is a mixture of ultralow HA with the molecular weight of 2kDa, low-molecular HA with the molecular weight of 250kDa, high-molecular HA with the molecular weight of 1200kDa and crosslinked HA, and the mass ratio of the ultralow HA, the low-molecular HA, the high-molecular HA and the crosslinked HA is 3:2:2: 2.
3. Preparation of content material liquid: putting 4kg of purified water and 0.01kg of vitamin C into a mixing tank, then adding 0.5kg of glycerol, then adding 3kg of peppermint oil, 1kg of menthol, 0.4kg of borneol, 4kg of eucalyptus oil, 1kg of lavender oil, 0.5kg of lemon essential oil, 0.008kg of vitamin E, 12kg of soybean oil and 2.5kg of beeswax, heating to 75 ℃, dissolving, stirring uniformly, and cooling to obtain a mixed oil material; grinding with colloid mill for 2 times to mix materials uniformly to obtain material liquid.
4. Preparing the slurry-blasting capsule: and (2) respectively putting the capsule skin liquid obtained in the step (2) and the content liquid obtained in the step (3) into a soft capsule machine containing the oral cavity maxilla-shaped die obtained in the step (1) under the environment of 20 ℃ and 50% of humidity to be pressed into pills, wherein the extrusion force is three quarters of that of a common soft capsule to obtain pulp-popping capsules, then carrying out shaping and drying on the produced pulp-popping capsules for 1.5 hours by a rolling cage type drying machine matched with the soft capsule machine, then taking out the capsules from a cage, washing the pills by edible ethanol with the volume fraction of 95%, airing the pills at the temperature of 25 ℃ and the humidity of 28% for 40 hours, then carrying out pill selection, and placing the finally selected pulp-popping capsules in a small drying tray and temporarily storing the capsules in a pre-drying room for later use.
Example 6
1. Making an oral cavity maxilla shape mould: firstly, obtaining an oral cavity contour model by adopting AFFINIS monoBody oral cavity impression material hydrophilic silicone rubber, cutting the oral cavity contour model along one third of the upper jaw vertical direction of the oral cavity contour model, and converting the oral cavity contour model into a ceramic model through 3D printing to obtain an oral cavity upper jaw shape model.
2. Preparing capsule shell liquid: putting 10kg of purified water, 0.6kg of hyaluronic acid, 3kg of glycerol and 10kg of gelatin into a gelatin melting tank in sequence, heating and heating for 30 minutes until the temperature is 75 ℃, keeping the temperature for 30 minutes, after the hyaluronic acid is completely dissolved and the gelatin is completely swelled and HAs no particles, pumping out bubbles and removing vacuum at the vacuum degree of 0.07Mpa, and discharging the gelatin through a pharmacopeia standard screen of 80 meshes to obtain capsule skin liquid, and keeping the temperature at 55 ℃ for later use, wherein the hyaluronic acid is a mixture of ultralow HA with the molecular weight of 4kDa, low-molecular HA with the molecular weight of 150kDa, high-molecular HA with the molecular weight of 1400kDa and crosslinked HA, and the mass ratio of the ultralow HA, the low-molecular HA, the high-molecular HA and the crosslinked HA is 4:3:1: 1.
3. Preparation of content material liquid: putting 3.5kg of purified water and 0.007kg of vitamin C into a mixing tank, then adding 1.8kg of glycerol, then adding 4kg of peppermint oil, 0.8kg of menthol, 0.3kg of borneol, 3kg of eucalyptus oil, 0.6kg of lavender oil, 1kg of lemon essential oil, 0.01kg of vitamin E, 16kg of soybean oil and 1.8kg of beeswax, heating to 75 ℃, dissolving, stirring uniformly, and cooling to obtain a mixed oil material; grinding with colloid mill for 3 times to mix materials uniformly to obtain material liquid.
4. Preparing the slurry-blasting capsule: and (2) respectively putting the capsule skin liquid obtained in the step (2) and the content liquid obtained in the step (3) into a soft capsule machine containing the oral cavity maxilla-shaped die obtained in the step (1) under the environment of 23 ℃ and 40% of humidity to be pressed into pills, wherein the extrusion force is three quarters of that of a common soft capsule to obtain pulp-popping capsules, then carrying out shaping and drying on the produced pulp-popping capsules for 1.5 hours by a rolling cage type drying machine matched with the soft capsule machine, then taking out the capsules from a cage, washing the pills by adopting edible ethanol with the volume fraction of 95%, airing the pills at the temperature of 23 ℃ and the humidity of 28% for 40 hours, then carrying out pill selection, and placing the finally selected pulp-popping capsules in a small drying tray and temporarily storing the capsules in a pre-drying room for later use.
Example 7
1. Making an oral cavity maxilla shape mould: firstly, obtaining an oral cavity contour model by adopting AFFINIS monoBody oral cavity impression material hydrophilic silicone rubber, cutting the oral cavity contour model along one third of the upper jaw vertical direction of the oral cavity contour model, and converting the oral cavity contour model into a ceramic model through 3D printing to obtain an oral cavity upper jaw shape model.
2. Preparing capsule shell liquid: putting 18kg of purified water, 2kg of hyaluronic acid, 8kg of glycerol and 18kg of gelatin into a gelatin melting tank in sequence, heating and heating for 30 minutes until the temperature is 75 ℃, keeping the temperature for 30 minutes, after the hyaluronic acid is completely dissolved and the gelatin is completely swelled and HAs no particles, pumping out bubbles under the vacuum degree of 0.07Mpa, relieving the vacuum, and discharging the gelatin through a pharmacopeia standard screen of 80 meshes to obtain capsule skin liquid, and keeping the temperature at 55 ℃ for later use, wherein the hyaluronic acid is a mixture of ultralow HA with the molecular weight of 5kDa, low-molecular HA with the molecular weight of 100kDa, high-molecular HA with the molecular weight of 1500kDa and crosslinked HA, and the mass ratio of the ultralow HA, the low-molecular HA, the high-molecular HA and the crosslinked HA is 1:1:3: 3.
3. Preparation of content material liquid: putting 4kg of purified water and 0.01kg of vitamin C into a mixing tank, then adding 1kg of glycerol, then adding 2kg of peppermint oil, 0.7kg of menthol, 0.5kg of borneol, 2kg of eucalyptus oil, 1kg of lavender oil, 1kg of lemon essential oil, 0.01kg of vitamin E, 15kg of soybean oil and 2kg of beeswax, heating to 75 ℃, dissolving, stirring uniformly, and cooling to obtain a mixed oil material; grinding with colloid mill for 3 times to mix materials uniformly to obtain material liquid.
4. Preparing the slurry-blasting capsule: and (2) respectively putting the capsule skin liquid obtained in the step (2) and the content liquid obtained in the step (3) into a soft capsule machine containing the oral cavity maxilla-shaped die obtained in the step (1) under the environment of 23 ℃ and 40% of humidity to be pressed into pills, wherein the extrusion force is three quarters of that of a common soft capsule to obtain pulp-popping capsules, then carrying out shaping and drying on the produced pulp-popping capsules for 1.5 hours by a rolling cage type drying machine matched with the soft capsule machine, then taking out the capsules from a cage, washing the pills by adopting edible ethanol with the volume fraction of 95%, airing the pills at the temperature of 23 ℃ and the humidity of 28% for 40 hours, then carrying out pill selection, and placing the finally selected pulp-popping capsules in a small drying tray and temporarily storing the capsules in a pre-drying room for later use.
Comparative example 1
Comparative example 1 and example 3 differ in that: comparative example 1 used an olive-shaped capsule mold.
Comparative example 2
Comparative example 2 and example 3 differ in that: the capsule shell liquid of comparative example 2 does not contain hyaluronic acid.
Comparative example 3
Comparative example 3 differs from example 3 in that: the hyaluronic acid of comparative example 3 did not contain ultra-low HA having a molecular weight of 3 kDa.
Comparative example 4
Comparative example 4 differs from example 3 in that: the hyaluronic acid of comparative example 4 did not contain low molecular HA having a molecular weight of 200 kDa.
Comparative example 5
Comparative example 5 differs from example 3 in that: the hyaluronic acid of comparative example 5 did not contain a high molecular weight HA having a molecular weight of 1300 kDa.
Comparative example 6
Comparative example 6 differs from example 3 in that: the hyaluronic acid of comparative example 6 contained no crosslinked HA.
TABLE 2 ingredient dosage table used in the examples
Experimental example 1
260 patients with xerostomia are selected from the group interior and staff relatives and observed, and the criteria of the selected cases are as follows: the age is 25-57 years old, and the nature is not limited.
The exclusion case criteria were: patients allergic to polysaccharides; patients have autoimmune deficiencies; other patients considered inappropriate for the test by the investigator.
Patients were randomized into 13 groups of 20 persons each, and each was fed the example and comparative samples.
1. After eating trial, the results related to the mechanical properties and release rate of the slurry-blasting capsules are shown in table 3, and the results of healing after eating trial are shown in table 3.
TABLE 3 mechanical Properties and Release Rate-related results of the popping capsules
Grouping | Automatic positioning | Speed of positioning | Surface smoothness | Hardness of | Time to rupture of film | Film adhesion time | Feeling of foreign body |
Example 1 | Accurate and accurate | 30s | Is not smooth | Is slightly hard | 5min | 10min | Can accept |
Example 2 | Accurate and accurate | 2s | Ultra-smooth | Too soft | 1min | 30min | Is not obvious |
Example 3 | Accurate and accurate | 10s | Is smooth and smooth | Is moderate | 3min | 20min | Is not obvious |
Example 4 | Accurate and accurate | 19s | Is smooth and smooth | Is moderate | 3min | 20min | Is not obvious |
Example 5 | Accurate and accurate | 11s | Is smooth and smooth | Is moderate | 3min | 20min | Is not obvious |
Example 6 | Accurate and accurate | 25s | Is not smooth | Is slightly hard | 5min | 11min | Can accept |
Example 7 | Accurate and accurate | 5s | Ultra-smooth | Too soft | 1min | 28min | Is not obvious |
Comparative example 1 | Inaccuracy of | 300s | Is smooth and smooth | Is moderate | 15min | 10min | Is obvious |
Comparative example 2 | Relatively accurate | 50s | Is not smooth | Too hard | 235min | 5min | Is obvious |
Comparative example 3 | Accurate and accurate | 10s | Is smooth and smooth | Is moderate | 8min | 40min | Is not obvious |
Comparative example 4 | Accurate and accurate | 10s | Is smooth and smooth | Is moderate | 6min | 35min | Is not obvious |
Comparative example 5 | Accurate and accurate | 10s | Is smooth and smooth | Is moderate | 3min | 10min | Is not obvious |
Comparative example 6 | Accurate and accurate | 10s | Is smooth and smooth | Is moderate | 2min | 5min | Is not obvious |
As can be seen from table 3, when the oral maxilla form molds according to the present invention (examples 1 to 7 and comparative examples 2 to 6) were used, accurate positioning was possible, whereas when the olive form mold (comparative example 1) was used, positioning was not accurate.
TABLE 4 curative effect after trial feeding
Grouping | Moisturizing effect | Mean time to cure | 15d cure rate |
Example 1 | 35min | 30d | 40% |
Example 2 | 40min | 25d | 45% |
Example 3 | 120min | 18d | 89% |
Example 4 | 122min | 18d | 88% |
Example 5 | 119min | 18d | 88% |
Example 6 | 40min | 28d | 42% |
Example 7 | 45min | 26d | 46% |
Comparative example 1 | 15min | 40d | 20% |
Comparative example 2 | 5min | 50d | 5% |
Comparative example 3 | 20min | 40d | 20% |
Comparative example 4 | 18min | 45d | 15% |
Comparative example 5 | 20min | 43d | 17% |
Comparative example 6 | 18min | 45d | 15% |
As can be seen from table 4, since the oral maxilla-shaped molds according to the present invention are used in examples 1 to 7 and hyaluronic acid is used, the moisturizing effect is good, the moisturizing time is up to 35min or more, the average cure time is short, below 30d, the cure rate of 15d is high and 40% or more, while the moisturizing effect of comparative examples 1 to 6 is poor, the average cure time is long, and the cure rate of 15d is low.
Comparing the comparative example 1 with the example 3, the difference is that the common soft capsule shape olive shape is used in the comparative example 1, because the olive shape soft capsule has poor fit with the oral cavity contour, positioning is difficult, membrane rupture is difficult, the membrane adhesion time is short, foreign body sensation is obvious, the moisturizing effect is poor, the cure time is long, and the cure rate is low after 15 days.
Comparing the comparative example 2 with the example 3, the difference is that the capsule skin liquid of the comparative example 2 does not contain hyaluronic acid, which results in poor smoothness of the capsule skin, difficult automatic positioning, large hardness, lasting shape retention, no influence on capsule skin rupture, short film adhesion time, obvious foreign body sensation, poor moisturizing effect, long healing time, and low 15d cure rate of only 5%.
The difference between the comparative example 3 and the example 3 is that the capsule skin liquid of the comparative example 3 does not contain ultralow HA, the capsule skin HAs moderate hardness, good shape retention, smooth surface after the capsule enters the oral cavity and meets residual water and saliva in the oral cavity, and high automatic positioning speed, but because the capsule skin liquid does not contain ultralow HA, the content of high molecular weight HA is relatively high, the capsule skin liquid is not beneficial to quick transdermal absorption and quick response of the effective components in the oral mucosa, so the capsule skin liquid HAs poor moisturizing effect, long average curing time and low 15d cure rate which is 20%.
The difference between the comparative example 4 and the example 3 is that the capsule skin liquid of the comparative example 4 does not contain low molecular HA with the molecular weight of 200kDa, although the capsule skin is matched with the outline of the oral cavity, because the capsule skin does not contain the low molecular HA, the high molecular content is higher, the quick transdermal absorption of the effective components on the oral mucosa is not facilitated, the quick response is realized, the moisturizing effect is poor, the average cure time is long, and the cure rate is low after 15 days.
The difference between the comparative example 5 and the example 3 is that the capsule skin liquid of the comparative example 5 does not contain macromolecular HA with the molecular weight of 1300kDa, and the capsule skin is matched with the oral contour, but because the capsule skin liquid does not contain macromolecular HA, the content of the low-molecular HA is higher, the effective components are quickly absorbed by the oral mucosa in a transdermal way, the acting time is short, the moisturizing effect is poor, the average curing time is long, and the 15d cure rate is low.
The difference between the comparative example 6 and the example 3 is that the capsule skin liquid of the comparative example 6 does not contain cross-linked HA, although the capsule skin HAs the contour fit degree with the oral cavity, because the capsule skin does not contain cross-linked HA, the content of low molecular HA is higher, the effective components can be quickly absorbed by the oral mucosa, the acting time is short, the moisturizing effect is poor, the average curing time is long, and the 15d cure rate is low.
In conclusion, as the hyaluronic acid has lubricity and moisture retention property, the uncrosslinked hyaluronic acid can be dissolved in the residual moisture in the oral cavity and the moisture in the saliva, the crosslinked hyaluronic acid swells in the residual moisture in the oral cavity and the moisture in the saliva, the small molecular hyaluronic acid can be quickly absorbed through the skin, the aquaporins on the surface of the mucous membrane are opened, the water can be quickly supplemented, the adhesion time of the large molecular weight hyaluronic acid and the crosslinked hyaluronic acid on the surface of the mucous membrane is long, the hyaluronic acid is dissolved in water to form a three-dimensional network structure, the small molecular content can be permeated through the three-dimensional network structure to take effect through the skin absorption on the mucous membrane of the oral cavity, the internal solute in the network structure can enhance the moisture retention effect of the hyaluronic acid, and the four kinds of hyaluronic acid are compounded according to a certain proportion, so that the burst pulp capsule disclosed by the invention can be used for, it is laminated in patient's oral cavity palace department position, can accurate location and long-term moisturizing.
The foregoing is directed to preferred embodiments of the present invention, other and further embodiments of the invention may be devised without departing from the basic scope thereof, and the scope thereof is determined by the claims that follow. However, any simple modification, equivalent change and modification of the above embodiments according to the technical essence of the present invention are within the protection scope of the technical solution of the present invention.
Claims (10)
1. An oral mucosa protection slurry burst capsule containing hyaluronic acid comprises a capsule skin and contents, wherein the capsule skin comprises hyaluronic acid, gelatin, glycerol and water;
the contents comprise oleum Menthae Dementholatum, Mentholum, Borneolum Syntheticum, oleum Eucalypti, oleum Lavandula Angustifolia, lemon essential oil, vitamin C, vitamin E, glycerol, soybean oil, Cera flava and water.
2. The popping capsule of claim 1, wherein said capsule shell comprises, by weight, 0.1-3 parts hyaluronic acid, 10-20 parts gelatin, 3-10 parts glycerol and 10-20 parts water, preferably said capsule shell comprises 0.6-2 parts hyaluronic acid, 10-18 parts gelatin, 3-8 parts glycerol and 10-18 parts water, more preferably said capsule shell comprises 1.0-1.5 parts hyaluronic acid, 13-16 parts gelatin, 4-7 parts glycerol and 13-16 parts water.
3. The popping capsule of claim 1 or 2 wherein the contents comprise, by weight, 0.5 to 5 parts of peppermint oil, 0.1 to 1 part of menthol, 0.1 to 0.5 part of borneol, 0.5 to 5 parts of eucalyptus oil, 0.1 to 1 part of lavender oil, 0.1 to 1 part of lemon essential oil, 0.001 to 0.01 part of vitamin C, 0.001 to 0.01 part of vitamin E, 0.5 to 2.5 parts of glycerin, 12 to 23 parts of soybean oil, 0.5 to 2.5 parts of beeswax and 1 to 4 parts of water; preferably, the content comprises 1.5-5 parts of peppermint oil, 0.5-1 part of menthol, 0.3-0.5 part of borneol, 1-5 parts of eucalyptus oil, 0.5-1 part of lavender oil, 0.3-1 part of lemon essential oil, 0.005-0.01 part of vitamin C, 0.006-0.01 part of vitamin E, 0.5-1.5 parts of glycerol, 12-18 parts of soybean oil, 1.5-2.5 parts of beeswax and 2-4 parts of water.
4. The burst capsule according to any one of claims 1 to 3, wherein the hyaluronic acid comprises ultra-low hyaluronic acid, low-molecular hyaluronic acid, high-molecular hyaluronic acid and cross-linked hyaluronic acid, preferably the mass ratio of ultra-low hyaluronic acid, low-molecular hyaluronic acid, high-molecular hyaluronic acid and cross-linked hyaluronic acid is 4-1:3-1:3-1:3-1, preferably 2:1:1: 1.
5. The popping capsule of claim 4 wherein,
the molecular weight of the ultra-low hyaluronic acid is 1k-10kDa, preferably 1k-5kDa, more preferably 1k-3 kDa;
the molecular weight of the low molecular weight hyaluronic acid is 100k-400kDa, preferably 100k-300kDa, more preferably 200k-300 kDa;
the molecular weight of the high molecular hyaluronic acid is 1000k-2000kDa, preferably 1000k-1500kDa, and more preferably 1000k-1300 kDa.
6. The popping capsule of any of claims 1-5 wherein the shape of said capsule is the same as the shape of the palate of the mouth.
7. A method for preparing oral mucosa protection plasma-explosion capsules containing hyaluronic acid comprises the following steps:
mixing hyaluronic acid, gelatin, glycerol and water, and defoaming to obtain capsule skin liquid;
mixing oleum Menthae Dementholatum, Mentholum, Borneolum Syntheticum, oleum Eucalypti, oleum Lavandula Angustifolia, lemon essential oil, vitamin C, vitamin E, glycerol, soybean oil, Cera flava and water to obtain content material liquid;
and pelleting the capsule skin liquid and the content liquid to obtain the capsule.
8. A method of using a capsule comprising placing the capsule of any one of claims 1-6 or the capsule of claim 7 in the mouth of a patient in need thereof, and fitting the capsule to the palate of the patient.
9. An oral care product comprising the popping capsule of any one of claims 1 to 6 or the popping capsule prepared by the preparation method of claim 7.
10. Use of the popping capsule according to any one of claims 1 to 6 or the popping capsule prepared by the preparation method according to claim 7 in the field of oral care, preferably in the field of dry mouth care, dry mouth itch care or mouth ulcer care.
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