CN111528516A - Nicotine-3, 5-dihydroxybenzoate compound crystal and application thereof in smokeless tobacco products - Google Patents
Nicotine-3, 5-dihydroxybenzoate compound crystal and application thereof in smokeless tobacco products Download PDFInfo
- Publication number
- CN111528516A CN111528516A CN202010366810.4A CN202010366810A CN111528516A CN 111528516 A CN111528516 A CN 111528516A CN 202010366810 A CN202010366810 A CN 202010366810A CN 111528516 A CN111528516 A CN 111528516A
- Authority
- CN
- China
- Prior art keywords
- nicotine
- dihydroxybenzoate
- parts
- crystal
- humectant
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
- A24B—MANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
- A24B15/00—Chemical features or treatment of tobacco; Tobacco substitutes, e.g. in liquid form
- A24B15/10—Chemical features of tobacco products or tobacco substitutes
- A24B15/16—Chemical features of tobacco products or tobacco substitutes of tobacco substitutes
-
- A—HUMAN NECESSITIES
- A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
- A24B—MANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
- A24B13/00—Tobacco for pipes, for cigars, e.g. cigar inserts, or for cigarettes; Chewing tobacco; Snuff
Abstract
The invention relates to a nicotine-3, 5-dihydroxybenzoate compound crystal and application thereof in smokeless tobacco products, belonging to the technical field of tobacco chemistry. The crystal has a molecular formula of C17H24N2O6Belonging to the monoclinic system, space group P21Unit cell parameters a =8.4365(6) Å, b =13.1486(11) Å, c =8.6019(5) Å =90.00 °, β =101.976(6) °, γ =90.00 °, V =933.42(12) Å3. The nicotine-3, 5-dihydroxybenzoate compound crystal obtained by the invention is used in a smokeless tobacco product instead of a nicotine monomer, compared with free nicotine, the pungency of protonated nicotine to oral cavity and respiratory tract is obviously reduced, higher nicotine concentration is realized in limited aerosol, and the toxicity of nicotine to human body is greatly reduced.
Description
Technical Field
The invention belongs to the technical field of tobacco chemistry, and particularly relates to a nicotine-3, 5-dihydroxybenzoate compound crystal and application thereof in smokeless tobacco products.
Background
With the change of life style and consumption concept of people and the rapid progress of science and technology, the demand and concern of tobacco consumers are constantly changed and are influenced by factors such as tobacco control policy, social public opinion guidance and the like, the development of traditional cigarettes is increasingly restricted, and the development of novel tobacco products becomes inevitable.
Among the novel tobacco products, smokeless tobacco products are those which are consumed by oral or nasal inhalation without combustion; in the use activity, it refers to a tobacco product that is not used in a smoking mode, comprising: oral tobacco (chewing tobacco, bagged buccal tobacco), dry snuff, wet snuff, paste tobacco, etc.
The smokeless tobacco product provides nicotine to human body by sucking, chewing and other ways. The form of nicotine introduction is critical in order to provide sustained physiological satisfaction.
Nicotine is a main chemical component of natural alkaloids in tobacco leaves, and the molecular structure of the nicotine is formed by two nitrogen heterocycles, wherein the pKa of a pyrrole ring is 7.87, and the pKa of a pyridine ring is 3.15. The nitrogen atom in the pyridine ring has weak basicity due to the influence of aromatization, and the basicity is similar to that of arylamine. At present, nicotine in gum chewing tobacco is mainly introduced by directly adding nicotine, and nicotine in bagged mouth tobacco is mainly introduced by tobacco sheets and tobacco powder. This presents three major problems: firstly, the discomfort of the digestive tract is caused by the overlarge stiffness; secondly, the release is too fast to provide continuous long-acting physiological satisfaction; thirdly, the taste is poor and the irritation is large. Therefore, in combination with the structural characteristics of nicotine, it is urgently needed to develop more systematic research on applicability before formulation around nicotine derivative preparation technology, nicotine release technology and the like, thereby laying theoretical and application technical foundations for formulation design, quality control and the like of novel tobacco products.
Disclosure of Invention
The invention aims to solve the defects of the prior art and provides a nicotine-3, 5-dihydroxybenzoate compound crystal and application thereof in smokeless tobacco products.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
in a first aspect, the present invention provides a nicotine-3, 5-dihydroxybenzoate compound crystal having a crystal molecular formula of: c17H24N2O6(ii) a The crystal belongs to a monoclinic system, space group P21The unit cell parameters are as follows:
α＝90.00°，β＝101.976(6)°，γ＝90.00°，
further, it is preferable that the crystal has an X-ray powder diffraction pattern having characteristic peaks at 2 θ angles of 10.64 °, 12.43 °, 13.30 °, 14.90 °, 17.07 °, 18.93 °, 21.31 °, 22.09 °, 22.48 °, 22.79 °, 24.25 °, 25.03 °, 25.47 °, 29.54 °.
Further, it is preferable that the liquid nuclear magnetic resonance of the crystal is1The chemical shifts of the H spectrum have characteristic peaks at 1.60, 1.77, 1.86, 2.07, 2.17, 2.25, 2.51, 3.13, 3.42, 6.41, 6.80, 7.35, 7.72, 8.46, 8.50 and 9.55 ppm.
Further, it is preferable that the number of asymmetric units Z in the unit cell of the crystal is 2, and the crystal density is 1.254g/cm3，R1＝0.0538，wR2＝0.0754。
The second aspect of the invention provides the application of the nicotine-3, 5-dihydroxybenzoate compound crystal in the preparation of smokeless tobacco products.
Further, preferably, the smokeless tobacco product is gum-based chewing tobacco or bagged buccal tobacco.
In a third aspect, the invention provides a chewing gum base tobacco containing the nicotine-3, 5-dihydroxybenzoate complex crystal, wherein the chewing gum base tobacco comprises a gum base, a sweetening agent, an acid-base modifier, a flavor, a food color, a humectant and the nicotine-3, 5-dihydroxybenzoate complex crystal;
wherein the weight part of the rubber matrix is 10-30 parts;
20-70 parts of a sweetening agent;
1-5 parts of an acid-base regulator;
0.5-5 parts of edible pigment;
1-5 parts of essence;
1-5 parts of a humectant;
the nicotine-3, 5-dihydroxybenzoate compound crystal accounts for 1-10% of the total mass of the gum base, the sweetening agent, the acid-base regulator, the essence, the edible pigment and the humectant.
Wherein the rubber matrix comprises one or a mixture of more of rubber, ester compounds and paraffin; the rubber is one or a mixture of more of gelatin, styrene-butadiene rubber, butyl rubber and polyisobutylene rubber; the esters are one or a mixture of more of rosin glyceride, rosin and polyvinyl acetate; the paraffin is one or a mixture of microcrystalline paraffin and solid edible paraffin, but is not limited thereto.
The edible pigment is selected from one or more of red yeast, chlorophyll, curcumin, carotene, amaranth, and caramel, but is not limited thereto.
Further, preferably, the acid-base regulator is sodium bicarbonate and/or sodium carbonate; the humectant is propylene glycol and/or glycerol.
The fourth aspect of the invention provides a bagged buccal cigarette containing the nicotine-3, 5-dihydroxybenzoate compound crystal, which comprises cellulose, water, sodium chloride, essence, an acid-base regulator, a sweetening agent, a humectant, an antioxidant and the nicotine-3, 5-dihydroxybenzoate compound crystal;
45-60 parts of cellulose;
10-30 parts of water;
3-5 parts of sodium chloride;
5-20 parts of essence;
1-5 parts of an acid-base regulator;
1-15 parts of a sweetening agent;
1-5 parts of a humectant;
1-5 parts of antioxidant;
wherein the mass of the nicotine-3, 5-dihydroxybenzoate compound crystal is 1-20% of the total mass of the cellulose, the water, the sodium chloride, the essence, the acid-base regulator, the sweetener, the humectant and the antioxidant.
Further, preferably, the acid-base regulator is sodium bicarbonate and/or sodium carbonate; the humectant is propylene glycol and/or glycerol; the antioxidant is one or more of vitamin A, vitamin C, vitamin E and tea polyphenols.
The cellulose includes: natural fibers, microcrystalline cellulose, cellulose derivatives, and mixtures thereof, but is not limited thereto.
The essence in the invention comprises one or more of lemon, mint, coffee, strawberry, blueberry, pineapple, peach, apple, orange, watermelon, red date, dark plum and fructus phyllanthi extract, but is not limited to the above.
The sweetener comprises: monosaccharides, disaccharides, trisaccharides, and polysaccharides, but are not limited thereto.
When a mixture is used, the present invention is not particularly limited to the ratio between the components.
Compared with the prior art, the invention has the beneficial effects that:
the nicotine-3, 5-dihydroxybenzoate compound crystal obtained by the invention is used in a smokeless tobacco product instead of a nicotine monomer, compared with free nicotine, the stimulation of protonated nicotine to oral cavity and respiratory tract is obviously reduced, higher nicotine concentration is realized in limited aerosol, and the absorption of nicotine-3, 5-dihydroxybenzoate in blood plasma is rapidly increased. In one aspect, tobacco products containing "nicotine complexes" can enhance smoker satisfaction by improving nicotine delivery in the blood and other sensory characteristics. On the other hand, the "bound nicotine" in smokeless tobacco products is absorbed into the blood at a rate comparable to free nicotine and as fast as conventional cigarettes. However, the delivery amount of nicotine does not exceed that of the traditional cigarette, so that the toxicity of nicotine to human bodies is greatly reduced.
The nicotine-3, 5-dihydroxybenzoate compound crystal of the invention shows obvious slow release effect in artificial simulated saliva, so that the compound crystal can be applied to the formulation design and quality control research of tobacco products in various forms, such as traditional cigarettes, cigars, electronic cigarettes, heating non-burning cigarettes and smokeless tobacco products, and provides more possibilities for the introduction form of nicotine.
The nicotine-3, 5-dihydroxybenzoate compound crystal is added into the gum base type chewing tobacco and the bagged mouth-sucking tobacco, so that the nicotine is uniformly, slowly and durably released in the oral cavity during consumption, the continuous and long-term physiological satisfaction of consumers is provided, the gastric irritation can be obviously reduced compared with the common gum base type chewing tobacco and bagged mouth-sucking tobacco containing nicotine or tobacco substances, the mouthfeel can be obviously improved, and the biological efficacy is good.
Drawings
FIG. 1 is a structural formula of nicotine-3, 5-dihydroxybenzoate complex crystal with atom numbering;
FIG. 2 is a crystal structure diagram of a single crystal of a nicotine-3, 5-dihydroxybenzoate complex;
FIG. 3 is a stacked view of the crystal structure of nicotine-3, 5-dihydroxybenzoate complex;
FIG. 4 is a liquid NMR of 3, 5-dihydroxybenzoic acid, nicotine and nicotine-3, 5-dihydroxybenzoate1H, spectrogram;
FIG. 5 is a graph comparing the IR spectra of 3, 5-dihydroxybenzoic acid with nicotine-3, 5-dihydroxybenzoate;
FIG. 6 is a graph of powder X-ray diffraction comparison of 3, 5-dihydroxybenzoic acid and nicotine-3, 5-dihydroxybenzoate.
Detailed Description
The present invention will be described in further detail with reference to examples.
It will be appreciated by those skilled in the art that the following examples are illustrative of the invention only and should not be taken as limiting the scope of the invention. The examples do not specify particular techniques or conditions, and are performed according to the techniques or conditions described in the literature in the art or according to the product specifications. The materials or equipment used are not indicated by manufacturers, and all are conventional products available by purchase.
Example 1
1. Preparation of nicotine-3, 5-dihydroxybenzoate complex crystals
1.1 preparation of Nicotine and 3, 5-Dihydroxybenzoic acid Complex
Taking 1.54g of 3, 5-dihydroxybenzoic acid in a conical flask, adding 20mL of pure water to completely dissolve the 3, 5-dihydroxybenzoic acid, stirring until the solid is completely dissolved, shading the conical flask, then placing the conical flask in an ultrasonic instrument, dropwise adding 1.6mL of nicotine, controlling the reaction temperature to be 40-45 ℃, finishing dropwise adding for 60min, and carrying out ultrasonic treatment until the reaction is finished. And shading the solution obtained by the reaction, and freeze-drying to obtain a powdery solid.
1.2 Complex Single Crystal culture
And (3) taking a proper amount of the solid obtained in the step (1.1), dropwise adding methanol until the solid is saturated, filtering, placing the filtrate in a place which is at normal temperature and is protected from light, standing, and obtaining a light yellow transparent blocky solid after crystals grow.
2. Structural characterization of nicotine-3, 5-dihydroxybenzoate complex crystals
2.1X-ray single crystal diffraction method
The measurement conditions were as follows: a crystal with a suitable size is selected, and an X-ray single crystal diffraction test is performed by using a CCD X-ray single crystal diffractometer (Bruker, Switzerland). MoKαAnd (3) radiation, wherein lambda is 0.71073, 293K and theta scans within the range of 6.156-52.736 degrees. The Olex2-1.1(SHELX-97) software package was used for structure resolution and refinement.
Structure analysis: x-ray single crystal diffraction structure analysis shows that the 3, 5-dihydroxy-benzoic acid nicotine compound consists of one univalent nicotine cation, one univalent 3, 5-dihydroxy-benzoic acid radical ion and 2 water molecules.
The compound belongs to a monoclinic system, P21Space group with density of 1.254g/cm3The specific unit cell parameters are shown in Table 1, the hydrogen bond data are shown in Table 2, the atom numbers are shown in FIG. 1, the crystal structures are shown in FIG. 2, and the stacking diagram of the crystal structures is shown in FIG. 3.
TABLE 1 cell parameters
TABLE 2 Long bond Angle results for hydrogen bonding in Nicotine-3, 5-dihydroxybenzoate
As can be seen from fig. 2, the complex plays an important role in the formation of its spatial structure in addition to being tightly bound by ionic bonds. 3, 5-dihydroxybenzoic acid molecule losing one H+Becomes monovalent 3, 5-dihydroxybenzoate anion (C)6H5O2-COO-) One of which is H+(O3-H) binds to the nitrogen (N2) on the pyrrole ring of the nicotine molecule to form-NH+The negative ion of the 3, 5-dihydroxy benzoate radical and the positive ion of the nicotine are tightly combined through ionic bonds. Meanwhile, the 3, 5-dihydroxybenzoate anions and the nicotine positive ions are indirectly connected through hydrogen bonding with water molecules (including O2-H.O 5, O1-H.O 6 and O6-H.N 1), so that the stability of the lattice structure is maintained. In addition, the 3, 5-dihydroxybenzoate ion maintains its stability in the crystal lattice through other intermolecular hydrogen bonds of the O6 atom.
As is apparent from the crystal structure stacking diagram (FIG. 3), the nicotine ions and the 3, 5-dihydroxybenzoate ions are tightly combined with each other, and the whole structure of the nicotine ions and the 3, 5-dihydroxybenzoate ions are alternately arranged in a wavy lamellar grid structure.
2.2 liquid Nuclear magnetic resonance Spectroscopy
And (3) testing conditions are as follows: the samples were measured at 298K using a Bruker-AVANCE III (400MHz) liquid NMR spectrometer1H-NMR. Samples of 5mg 3, 5-dihydroxybenzoic acid, 5. mu.L nicotine and 5mg nicotine-3, 5-dihydroxybenzoic acid were weighed out separately and dissolved in 500. mu.L DMSO-d6In a solvent. Nuclear magnetic resonance data were processed and analyzed using Topspin 3.5 software (Bruker Biospin, L td.).
The nuclear magnetic spectra of nicotine, 3, 5-dihydroxybenzoic acid and nicotine-3, 5-dihydroxybenzoic acid are shown in figure 4, the molecular structures and atom numbers of nicotine and 3, 5-dihydroxybenzoic acid are shown in figure 4, and the molecular structures and atom numbers of nicotine-3, 5-dihydroxybenzoic acid are shown in figure 1. Nicotine:1H-NMR(400MHz，DMSO-d6)，:8.47(d,1H,C5-H),8.45(d,1H,C1-H),7.72(d,1H,C3-H),7.35(q,1H,C2-H),3.15(t,1H,C9-Ha),3.09(t,1H,C6-H),2.25(t,1H,C9-Hb),2.16(m,1H,C7-Hb),2.06(s,3H,CH3),1.84(m,1H,C8-Ha),1.75(m,1H,C8-Hb),1.58(m,1H,C7-Ha). 3, 5-dihydroxybenzoic acid:1H-NMR(400MHz，DMSO-d6)，:12.65(s,1H,-COOH),9.54(s,2H,O1-H,O2-H),6.80(d,2H,C2-H,C6-H),6.41(t,1H,C4-H). Nicotine-3, 5-dihydroxybenzoic acid salt:1H-NMR(400MHz，DMSO-d6)，:9.55(s,2H,O1-H,O2-H),8.50(d,1H,C2-H),8.45(q,1H,C3-H),7.72(m,1H,C5-H),7.35(q,1H,C4-H),6.80(d,2H,C12-H,C16-H),6.41(t,1H,C14-H),3.13(m,2H,C9-Ha,C6-H),2.25(q,1H,C9-Hb),2.16(m,1H,C7-Hb),2.07(s,3H,CH3),1.85(m,1H,C8-Ha),1.76(m,1H,C8-Hb),1.59(m,1H,C7-Ha)。
comparing the nuclear magnetic spectrograms of the products of the 3, 5-dihydroxybenzoic acid and the nicotine-3, 5-dihydroxybenzoic acid, the characteristic peak corresponding to the carboxyl hydrogen in the 3, 5-dihydroxybenzoic acid in the nuclear magnetic spectrum of the products disappears, which shows that the reaction of the nicotine and the 3, 5-dihydroxybenzoic acid occurs and the carboxyl hydrogen in the acid is dissociated. Comparing the nuclear magnetic spectra of nicotine and nicotine-3, 5-dihydroxybenzoate product, and comparing the nuclear magnetic spectrum of the product with C corresponding to nicotine6The H peak shifts from 3.09 to 3.13, Δ 0.04; c in the product close to the nitrogen of the pyrrole ring3-H also undergoes a chemical shift change of 0.03; meanwhile, the hydrogen on the nicotine pyrrole ring generates weak chemical shift changes with different degrees. In conclusion, it is shown from the nuclear magnetic hydrogen spectrum result analysis that 3, 5-dihydroxybenzoic acid reacts with nicotine and the chemical shift of hydrogen on pyridine ring is obviously changed, so that it can be speculated that nicotine reacts with 3, 5-dihydroxybenzoic acid in acid-base manner and nitrogen on pyrrole ring of nicotine passes through to react with nicotineCarboxyl group of 3, 5-dihydroxybenzoic acid.
2.3 Infrared Spectroscopy
And (3) testing conditions are as follows: a fourier transform infrared spectrometer (Nicolet670) from siemer feishol technologies, usa was used. Fully grinding and mixing a sample to be tested and dry KBr, tabletting, and setting the test range to be 4000--1The number of scans was 64.
The analysis result is shown in figure 5, the infrared spectrum of the 3, 5-dihydroxy benzoic acid nicotine salt product is different from the superposition of the 3, 5-dihydroxy benzoic acid spectrum and the nicotine spectrum, which indicates that the product is not a physical mixture of 3, 5-dihydroxy benzoic acid and nicotine. 3, 5-Dihydroxybenzoic acid at 1710cm-1Strong peak at, and 920cm-1The broad peak is the characteristic peak of the carboxylic acid dimer, and the spectrum of the 3, 5-dihydroxybenzoic acid nicotine salt and the 3, 5-dihydroxybenzoic acid is compared, the peak intensities of the two characteristic peaks are obviously weakened and almost disappear, which shows that the content of the carboxylic acid dimer in the product is weak, further shows that the carboxyl of the 3, 5-dihydroxybenzoic acid is combined with nicotine, thereby greatly weakening the ratio of the carboxylic acid dimer.
2.4 powder X-ray diffraction Pattern (PXRD)
And (3) testing conditions are as follows: grinding 3, 5-dihydroxybenzoic acid and crystalline 3, 5-dihydroxybenzoic acid nicotine salt samples to be tested. X-ray powder diffractometer: pasacaceae, Inc. (Netherlands). The one-dimensional detection system X' Pert-PRO hyper energy detector, Cu ka radiation, IK α 2, IK α 1 0.5, λ 1 1.540598, λ 2 1.544426, tunnel voltage 40kV, tube current 40mA, 2 θ scan range 4-50 °, step 0.02626(2 θ), count time 30 ms/step. FIG. 6 shows PXRD spectra of 3, 5-dihydroxybenzoic acid and 3, 5-dihydroxybenzoic acid nicotine salt. Compared with PXRD spectrograms of 3, 5-dihydroxybenzoic acid and 3, 5-dihydroxybenzoic acid nicotine salt, the significant change of characteristic peak positions (shown in table 3) can be seen, the characteristic peak positions of the two are obviously different, and the result that the 3, 5-dihydroxybenzoic acid reacts with nicotine to generate nicotine-3, 5-dihydroxybenzoic acid is proved.
TABLE 33 XRPD Main Peak positions of 5, 5-Dihydroxybenzoic acid and Nicotine-3, 5-Dihydroxybenzoates
Example 2
A gum base type chewing tobacco containing the nicotine-3, 5-dihydroxybenzoate compound crystal, wherein the gum base type chewing tobacco comprises gum base, sweetener, pH regulator, essence, edible pigment, humectant and nicotine-3, 5-dihydroxybenzoate compound crystal;
wherein the weight part of the rubber matrix is 10 parts;
20 parts of sweetening agent;
1 part of acid-base regulator;
0.5 part of edible pigment;
the essence accounts for 1 part by weight;
the weight portion of the humectant is 1 portion;
the nicotine-3, 5-dihydroxy benzoate compound crystal accounts for 1% of the total mass of the gum base, the sweetener, the acid-base regulator, the essence, the edible pigment and the humectant.
The acid-base regulator is sodium bicarbonate; the humectant is propylene glycol.
Example 3
A gum base type chewing tobacco containing the nicotine-3, 5-dihydroxybenzoate compound crystal, wherein the gum base type chewing tobacco comprises gum base, sweetener, pH regulator, essence, edible pigment, humectant and nicotine-3, 5-dihydroxybenzoate compound crystal;
wherein the weight part of the rubber matrix is 30 parts;
the weight portion of the sweetener is 70 portions;
the weight portion of the acid-base regulator is 5 portions;
the weight portion of the edible pigment is 5 portions;
the essence accounts for 5 parts by weight;
the humectant accounts for 5 parts by weight;
the nicotine-3, 5-dihydroxy benzoate compound crystal accounts for 10% of the total mass of the gum base, the sweetener, the acid-base regulator, the essence, the edible pigment and the humectant.
The acid-base regulator is sodium carbonate; the humectant is glycerol.
Example 4
A gum base type chewing tobacco containing the nicotine-3, 5-dihydroxybenzoate compound crystal, wherein the gum base type chewing tobacco comprises gum base, sweetener, pH regulator, essence, edible pigment, humectant and nicotine-3, 5-dihydroxybenzoate compound crystal;
wherein the weight part of the rubber matrix is 15 parts;
60 parts of sweetening agent;
the weight portion of the acid-base regulator is 2 portions;
the weight portion of the edible pigment is 3 portions;
2 parts of essence;
the humectant accounts for 3 parts by weight;
the nicotine-3, 5-dihydroxy benzoate compound crystal accounts for 5% of the total mass of the gum base, the sweetener, the acid-base regulator, the essence, the edible pigment and the humectant.
The acid-base regulator is sodium bicarbonate and sodium carbonate (the mass ratio is 1: 1); the humectant is propylene glycol and glycerol (mass ratio is 1: 1).
The gum base is styrene-butadiene rubber, the sweetening agent is glucose, the edible pigment is carotene, and the essence is lemon essence.
Example 5
A bagged buccal cigarette containing nicotine-3, 5-dihydroxybenzoate compound crystal comprises cellulose, water, sodium chloride, essence, pH regulator, sweetener, humectant, antioxidant and nicotine-3, 5-dihydroxybenzoate compound crystal;
45 parts of cellulose;
10 parts of water;
3 parts of sodium chloride;
the essence accounts for 5 parts by weight;
1 part of acid-base regulator;
the weight portion of the sweetening agent is 1 portion;
the weight portion of the humectant is 1 portion;
1 part of antioxidant;
wherein the mass of the nicotine-3, 5-dihydroxy benzoate compound crystal is 1 percent of the total mass of the cellulose, the water, the sodium chloride, the essence, the acid-base regulator, the sweetener, the humectant and the antioxidant.
The acid-base regulator is sodium bicarbonate; the humectant is propylene glycol; the antioxidant is vitamin A.
Example 6
A bagged buccal cigarette containing nicotine-3, 5-dihydroxybenzoate compound crystal comprises cellulose, water, sodium chloride, essence, pH regulator, sweetener, humectant, antioxidant and nicotine-3, 5-dihydroxybenzoate compound crystal;
the weight portion of the cellulose is 60 portions;
the weight portion of water is 30 portions;
5 parts of sodium chloride;
20 parts of essence;
the weight portion of the acid-base regulator is 5 portions;
15 parts of sweetening agent;
the humectant accounts for 5 parts by weight;
the antioxidant accounts for 5 parts by weight;
wherein the mass of the nicotine-3, 5-dihydroxybenzoate compound crystal is 20% of the total mass of the cellulose, the water, the sodium chloride, the essence, the pH regulator, the sweetener, the humectant and the antioxidant.
The acid-base regulator is sodium bicarbonate and sodium carbonate (the mass ratio is 1: 1); the humectant is propylene glycol and glycerol (mass ratio is 1: 1); the antioxidant is vitamin E and tea polyphenols (mass ratio is 1: 1).
Example 7
A bagged buccal cigarette containing nicotine-3, 5-dihydroxybenzoate compound crystal comprises cellulose, water, sodium chloride, essence, pH regulator, sweetener, humectant, antioxidant and nicotine-3, 5-dihydroxybenzoate compound crystal;
the weight portion of the cellulose is 56 portions;
the weight portion of water is 20 portions;
4 parts of sodium chloride;
the essence accounts for 10 parts by weight;
the weight portion of the acid-base regulator is 2 portions;
3 parts of sweetening agent;
the weight portion of the humectant is 2 portions;
the antioxidant accounts for 3 parts by weight;
wherein the nicotine-3, 5-dihydroxybenzoate compound crystal is 10% of total mass of cellulose, water, sodium chloride, essence, pH regulator, sweetener, humectant, and antioxidant.
The acid-base regulator is sodium carbonate; the humectant is glycerol; the antioxidant is vitamin C.
The cellulose is microcrystalline cellulose, the essence is peppermint essence, and the sweetener is aspartame.
Comparative example 1
The same chewing tobacco of gum base type was prepared and formulated as in example 4, except that nicotine was used instead of the nicotine-3, 5-dihydroxybenzoate complex crystals of example 4.
The organization-related suckers smoked the example 4 and the comparative example 1 products in comparison according to the "gum base type chewing tobacco sensory evaluation criteria" and scored as shown in table 1 below (higher score for the corresponding index is better). The chewing tobacco of gum base type with added nicotine-3, 5-dihydroxybenzoate complex crystal was superior to chewing tobacco of gum base type with directly added nicotine in both physiological and pleasurable aspects, especially the example 4 product was significantly better in pleasurable aspect than the comparative example 1 product, and the overall sustained satisfaction and mouthfeel were better.
Table 1 table of original records of gum base type chewing tobacco sensory quality evaluation
Comparative example 2
The same pouched mouth-holding cigarette was made, with the same formulation as in example 7, but with tobacco powder instead of the nicotine-3, 5-dihydroxybenzoate complex crystals of example 7.
The samples of the products of example 7 and comparative example 2 were comparatively smoked by the organization-related smoking experts according to the sensory evaluation standard of bagged buccal cigarettes, and the scores were given as shown in table 2 and table 2 below (the higher the score, the better the corresponding index). The bagged mouth-sucking cigarette added with the nicotine-3, 5-dihydroxybenzoate compound crystal is better than the bagged mouth-sucking cigarette directly added with tobacco powder in the aspects of duration of satisfaction, coordination, irritation, comfort, cleanliness and the like, especially the product in the comfort is obviously better than the product in the comparative example 2, and the overall mouth feeling is better.
TABLE 2 original recording table for sensory quality evaluation of bagged buccal tobacco
Table 2 original recording table for sensory quality evaluation of bagged mouth tobacco
The foregoing shows and describes the general principles, essential features, and advantages of the invention. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are described in the specification and illustrated only to illustrate the principle of the present invention, but that various changes and modifications may be made therein without departing from the spirit and scope of the present invention, which fall within the scope of the invention as claimed. The scope of the invention is defined by the appended claims and equivalents thereof.
Claims (10)
1. A nicotine-3, 5-dihydroxybenzoate compound crystal is characterized in that the molecular formula of the crystal is as follows: c17H24N2O6(ii) a The crystal belongs to a monoclinic system, space group P21Unit cell parameters a =8.4365(6) Å, b =13.1486(11) Å, c =8.6019(5) Å =90.00 °, β =101.976(6) °, γ =90.00 °, V =933.42(12) Å3。
2. A nicotine-3, 5-dihydroxybenzoate complex crystal according to claim 1, characterized in that said crystal has an X-ray powder diffraction pattern with characteristic peaks at 2 Θ angles of 10.64 °, 12.43 °, 13.30 °, 14.90 °, 17.07 °, 18.93 °, 21.31 °, 22.09 °, 22.48 °, 22.79 °, 24.25 °, 25.03 °, 25.47 °, 29.54 °.
3. The nicotine-3, 5-dihydroxybenzoate complex crystal of claim 1, characterized in that said crystal has liquid nuclear magnetic resonance1The chemical shifts of the H spectrum have characteristic peaks at 1.60, 1.77, 1.86, 2.07, 2.17, 2.25, 2.51, 3.13, 3.42, 6.41, 6.80, 7.35, 7.72, 8.46, 8.50 and 9.55 ppm.
4. A nicotine-3, 5-dihydroxybenzoate complex crystal according to claim 1, characterized in that said crystal has an asymmetric unit number Z =2 in the unit cell and a crystal density of 1.254g/cm3，R1=0.0538，wR2=0.0754。
5. Use of the nicotine-3, 5-dihydroxybenzoate complex crystal according to any of claims 1 to 4 for the preparation of a smokeless tobacco product.
6. Use of the nicotine-3, 5-dihydroxybenzoate complex crystal according to claim 5 in the preparation of a smokeless tobacco product, wherein said smokeless tobacco product is a gum-based chewing tobacco or a pouched mouth tobacco.
7. A chewing gum based on gum containing the nicotine-3, 5-dihydroxybenzoate complex crystal according to any of claims 1-4, characterized in that: the chewing tobacco of gum base type comprises a gum substrate, a sweetening agent, an acid-base regulator, essence, edible pigment, a humectant and nicotine-3, 5-dihydroxybenzoate compound crystals;
wherein the weight part of the rubber matrix is 10-30 parts;
20-70 parts of a sweetening agent;
1-5 parts of an acid-base regulator;
0.5-5 parts of edible pigment;
1-5 parts of essence;
1-5 parts of a humectant;
the nicotine-3, 5-dihydroxybenzoate compound crystal accounts for 1-10% of the total mass of the gum base, the sweetening agent, the acid-base regulator, the essence, the edible pigment and the humectant.
8. A chewing gum based tobacco containing crystals of nicotine-3, 5-dihydroxybenzoate complex according to claim 7, characterized in that: the pH regulator is sodium bicarbonate and/or sodium carbonate; the humectant is propylene glycol and/or glycerol.
9. A pouched mouth-holding cigarette containing the nicotine-3, 5-dihydroxybenzoate compound crystal according to any of claims 1 to 4, characterized in that: the bagged buccal cigarette comprises cellulose, water, sodium chloride, essence, an acid-base regulator, a sweetening agent, a humectant, an antioxidant and a nicotine-3, 5-dihydroxybenzoate compound crystal;
45-60 parts of cellulose;
10-30 parts of water;
3-5 parts of sodium chloride;
5-20 parts of essence;
1-5 parts of an acid-base regulator;
1-15 parts of a sweetening agent;
1-5 parts of a humectant;
1-5 parts of antioxidant;
wherein the mass of the nicotine-3, 5-dihydroxybenzoate compound crystal is 1-20% of the total mass of the cellulose, the water, the sodium chloride, the essence, the acid-base regulator, the sweetener, the humectant and the antioxidant.
10. The pouched buccal cigarette containing nicotine-3, 5-dihydroxybenzoate complex crystals of claim 9, wherein: the pH regulator is sodium bicarbonate and/or sodium carbonate; the humectant is propylene glycol and/or glycerol; the antioxidant is one or more of vitamin A, vitamin C, vitamin E and tea polyphenols.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010366810.4A CN111528516A (en) | 2020-04-30 | 2020-04-30 | Nicotine-3, 5-dihydroxybenzoate compound crystal and application thereof in smokeless tobacco products |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010366810.4A CN111528516A (en) | 2020-04-30 | 2020-04-30 | Nicotine-3, 5-dihydroxybenzoate compound crystal and application thereof in smokeless tobacco products |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111528516A true CN111528516A (en) | 2020-08-14 |
Family
ID=71973501
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010366810.4A Pending CN111528516A (en) | 2020-04-30 | 2020-04-30 | Nicotine-3, 5-dihydroxybenzoate compound crystal and application thereof in smokeless tobacco products |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111528516A (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3845217A (en) * | 1972-11-16 | 1974-10-29 | Helsingborg L Ab | Buffered smoking substitute compositions |
| CN106536501A (en) * | 2014-05-27 | 2017-03-22 | R.J.雷诺兹烟草公司 | Nicotine salts, co-crystals, and salt co-crystal complexes |
| CN108285441A (en) * | 2018-01-03 | 2018-07-17 | 云南中烟工业有限责任公司 | A kind of nicotine-mandelate compound crystal, preparation method and the tobacco product comprising it |
| CN108495563A (en) * | 2015-11-25 | 2018-09-04 | R.J.雷诺兹烟草公司 | Nicotine salt, eutectic and salt eutectic complex |
| CN110393307A (en) * | 2019-09-05 | 2019-11-01 | 深圳市真味生物科技有限公司 | A kind of smokeless tobacco tar and preparation method thereof |
| CN110437204A (en) * | 2019-09-05 | 2019-11-12 | 深圳市真味生物科技有限公司 | A kind of electronics tobacco tar of nicotine salt and its preparation method and application the nicotine salt |
-
2020
- 2020-04-30 CN CN202010366810.4A patent/CN111528516A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3845217A (en) * | 1972-11-16 | 1974-10-29 | Helsingborg L Ab | Buffered smoking substitute compositions |
| CN106536501A (en) * | 2014-05-27 | 2017-03-22 | R.J.雷诺兹烟草公司 | Nicotine salts, co-crystals, and salt co-crystal complexes |
| CN108495563A (en) * | 2015-11-25 | 2018-09-04 | R.J.雷诺兹烟草公司 | Nicotine salt, eutectic and salt eutectic complex |
| CN108285441A (en) * | 2018-01-03 | 2018-07-17 | 云南中烟工业有限责任公司 | A kind of nicotine-mandelate compound crystal, preparation method and the tobacco product comprising it |
| CN110393307A (en) * | 2019-09-05 | 2019-11-01 | 深圳市真味生物科技有限公司 | A kind of smokeless tobacco tar and preparation method thereof |
| CN110437204A (en) * | 2019-09-05 | 2019-11-12 | 深圳市真味生物科技有限公司 | A kind of electronics tobacco tar of nicotine salt and its preparation method and application the nicotine salt |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20210122728A1 (en) | Nicotine salts, co-crystals, and salt co-crystal complexes | |
| EP3214956B1 (en) | Solution comprising nicotine in unprotonated form and protonated form | |
| US11225468B2 (en) | Nicotine salts, co-crystals, and salt co-crystal complexes | |
| EP3379952B1 (en) | Nicotine salts, co-crystals, and salt co-crystal complexes | |
| CN108323792B (en) | Nicotine-gentisate compound crystal, preparation method thereof and tobacco product containing nicotine-gentisate compound crystal | |
| CN108285441A (en) | A kind of nicotine-mandelate compound crystal, preparation method and the tobacco product comprising it | |
| US20050053665A1 (en) | Nicotine formulations and use thereof | |
| CN108329296A (en) | A kind of nicotine-tartrate compound crystal, preparation method and the tobacco product comprising it | |
| CN103494324A (en) | Bagged snus and manufacturing method thereof | |
| CN111072629A (en) | Nicotine-oxalate compound crystal and application thereof | |
| RU2770248C1 (en) | Aerosol-forming composition | |
| CA2868445C (en) | Nicotine formulation | |
| JP2022548626A (en) | nicotine pouch | |
| CN111528516A (en) | Nicotine-3, 5-dihydroxybenzoate compound crystal and application thereof in smokeless tobacco products | |
| CN108323791B (en) | Nicotine-zinc oxide compound, preparation method thereof and tobacco product containing nicotine-zinc oxide compound | |
| SU849980A4 (en) | Method of producing smoked mixture | |
| CA2366845A1 (en) | Composition for medicated chewing gums, process for manufacturing the same and tablets so obtained | |
| CN111393410B (en) | Preparation method of nicotine-3, 5-dihydroxybenzoate and application of nicotine-3, 5-dihydroxybenzoate in electronic cigarette | |
| JP4566128B2 (en) | Method for producing crystalline polymorph of irinotecan hydrochloride | |
| CN111084410A (en) | Preparation method and application of nicotine-oxalate compound crystal | |
| CN111528515A (en) | Tobacco reconstituted tobacco containing nicotine-3, 5-dihydroxybenzoate and application thereof | |
| JP7454880B2 (en) | Oral rinse composition for alleviating xerostomia containing a polyethylene glycol derivative as an active ingredient | |
| RU2787865C2 (en) | Gel and crystalline powder | |
| CN113647666B (en) | Preparation method of heated cigarette | |
| KR20230074513A (en) | Determination of thyroid hormone β receptor agonists, methods for their preparation and uses thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |